Category Archives: Epigenetic Factors to Reduce Breast Cancer Risk

Epigenetic Factors to Reduce Breast Cancer Risk – Part 4

Epigenetic Factors to Reduce Breast Cancer Risk – Part 4

My goal, in this series of articles, is to empower you with information about epigenetic factors that can be utilized to not only reduce your risk of breast cancer, but also to help you heal from breast cancer should you be diagnosed with it.

For more information on my personal reasons for putting this information together, see Part 1 of the series, Epigenetic Factors To Reduce Breast Cancer Risk Part 1.

This article, Part 4 of the series, will cover the phytonutrients that ease or prevent cancer-promoting inflammation. Chronic inflammation in the body is a known risk factor for various cancers, including breast cancer. Eliminating inflammation is a valid strategy for both preventing cancer and for helping to treat it. Science recognizes this and, indeed, many anti-inflammatory cancer drugs are also used to treat inflammatory diseases such as rheumatoid arthritis. [1]

Once a cell becomes malignant, inflammation is a powerful promoter of cancer. Fortunately for us, nature provides us with hundreds of natural anti-inflammatory phytochemicals that work at the gene level to counter inflammation. Here are some of the best ones.

PART 4 – NUTRIENTS THAT EASE OR PREVENT CANCER-PROMOTING INFLAMMATION

Alpha-amyrin, beta-amyrin – found in certain plants including Launaea procumbens, hemp seeds, sunflower seeds [2]

Alpha-linolenic acid (ALA), an omega 3 fat found in buckwheat bran, chia, chickpeas, flaxseed, green beans, hemp seeds, macadamia nuts, pecans, pistachio nuts, pumpkin seeds, quinoa, red beans, soybeans, walnuts [3]

Anthocyanins, plant pigments, found in acai, Anasazi beans, apples, black beans, bilberries, black raspberries, black rice, blackcurrants, blueberries, chickpeas, elderberries, grapes, pomegranates, purple beans, purple carrots, purple sweet potatoes, sorghum bran, strawberries, walnuts [4], [5]

Apigenin, a flavonoid found in celery, chamomile tea, chickpeas,  clove, grapefruit, onions, oranges, parsley, peppermint, rice bran, sorghum bran [6], [7]

Berberine, an alkaloid found in goldenseal, barberry, Oregon grape, Huang bai, tree turmeric [8], [9]

Beta-sitosterol, a plant sterol found in almonds, amaranth, barley, black rice, Brazil nuts, flaxseed, hemp seed, macadamia nuts, oats, pecans, pistachio nuts, pumpkin seeds, quinoa, rice bran, sesame seeds, soybeans, sunflower seeds, walnuts, wheat, wheat bran [10], [11]

Betaine, an amino acid created in the body from choline and glycine. Found in amaranth, barley, beef, beets, oats, quinoa, spinach, sunflower seeds, sweet potato, wheat, wheat bran [12], [13]

Bio-chanin A, an isoflavone found in alfalfa sprouts, astragalus, cashews, chickpeas, kidney beans, pinto beans, red clover [14], [15]

Caffeic acid, a polyphenol found in adzuki beans, apples, apicots, barley, bee propolis, buckwheat bran, brown rice, chia seeds, chickpeas, coffee, flaxseed, goji/wolfberry, hazelnuts, lentils, oats, quinoa, sorghum bran, soybeans, sunflower seeds, wheat [16], [17]

Capsaicin, a phytochemical in hot chili peppers, cayenne [18], [19]

Catechins and epicatechins, polyphenols found in adzuki beans, almonds, amaranth, apricots, bilberries, buckwheat bran, chickpeas, green beans, green tea, lentils, pecans, sorghum bran, wheat bran [17], [20]

Chlorophyll, a plant pigment found in all green plants and herbs, blue-green algae, grapes, green beans, matcha tea, pistachio nuts, pumpkin seeds, seaweed, spirulina, sprouts, wheatgrass [21]

Conjugated Linoleic Acid (CLA), from (preferably) organic grass fed beef, butter from grass-fed cows raised organically, full fat (preferably raw) dairy products like cream, milk, yogurt or cheese [22], [23], [24]

Curcumin, the active phytochemical polyphenol in turmeric [25], [26], [27]

Ellagic acid, a polyphenol found in apples, black raspberries, blackberries, Brazil nuts, cranberries, pomegranates, pecans, raspberries, strawberries, walnuts [28]

Essential oils – many essential oils have potent anti-inflammatory activity, including:
Basil [29]
Black Pepper [30]
Cedarwood [31]
Cinnamon [32]
Citrus essential oils [33]
Clove [34]
Copaiba [35]
Frankincense [36]
Ginger [37]
Lavender [38]
Myrrh [36]
Rosemary [39]
Ylang ylang [40]

Fiber, found in beans, bran, whole grains, nuts and seeds, is associated with decreasing systemic inflammation [41], [42]

Gamma linolenic acid (GLA), an omega-6 fatty acid found in barley, blackcurrant seed oil, borage seed oil, evening primrose oil, hemp seeds, oats, spirulina [43], [37]

Genistein, an isoflavone found in chickpeas, kidney beans, quinoa, soybeans [44], [45]

Ginger, as the root, powder and essential oil form [37]

Glucosinolates, sulforaphane and isothiocyanates – phytochemicals found in Brassica vegetables including arugula (rocket), bok choy, broccoli, broccoflower, Brussels sprouts, cabbage, cauliflower, collard greens, daikon, horseradish, kale, kohlrabi, mizuna, mustard greens, mustard seeds, radishes, rutabaga, tatsoi, turnips, wasabi, watercress [46], [47]

Kaempferol, a flavonoid found in Anasazi beans, barley, black beans, black rice, buckwheat bran, chickpeas, chia seeds, flaxseed, green beans, lentils, quinoa, red beans, rice bran [48], [49]

Luteolin, a flavonoid found in celery, lemongrass, lentils, oregano, parsley, peppermint, rice bran, rosemary, sorghum bran [50], [51]

Naringenin, a flavonoid found in almonds, all citrus fruit, black rice, rice bran, sorghum bran [52], [53]

Omega-3 fatty acids, found in chia seeds, Brussels sprouts, flax seeds, hemp seeds, kiwi fruit, lingonberries, perilla seed oil, walnuts [54], [55]

Protocatechuic acid, a polyphenol found in acai, adzuki beans, apples, avocados, bilberries, blackberries, blueberries, brown rice, buckwheat, cauliflower, dates, eggplant, garlic, hazelnuts, kiwi, lentils, mango, mangosteen, mulberries, olive oil, olives, pears, pistachio nuts, raspberries, red onion, sorghum bran, strawberries, wheat [56]. [57]

Quercetin, a polyphenol found in adzuki beans, Anasazi beans, apples, apricots, asparagus, barley, berries, black beans, black rice, broccoli, capers, cauliflower, celery, chickpeas, chia seeds, eggplant, gingko biloba, grapes, green beans, green pepper, honey, kale, lentils, lettuce, onions, quinoa, red onions, shallots, tea (black and green), tomatoes [58], [59]

Resveratrol, part of a group of polyphenol compounds found in blueberries, cranberries, dark chocolate, peanuts, peanut butter, pistachio nuts, grapes, black beans, lentils, red wine, white wine [60], [61]

Saponins, triterpenoid phytochemicals found in amaranth, Anasazi beans, asparagus, barley, black beans, chickpeas, green beans, green soybeans, jiaogulan, oats, panax ginseng, quinoa, red beans, spinach, sunflower seeds, tomatoes, wheat [62], [63]

Selenium, a mineral found in amaranth, barley, Brazil nuts, brewer’s yeast, broccoli, brown rice, buckwheat bran, chickpeas, chicken, garlic, kelp, lentils, liver, macadamia nuts, molasses, oats, onions, pecans, pistachio nuts, pumpkin seeds, quinoa, red beans, salmon, seafood, spelt, sunflower seeds, walnuts, wheat, wheat bran, wheat germ [64], [65]

Vitamin D3 – known as the sunshine vitamin because when sunlight hits your skin, a chemical reaction takes place which stimulates the production of vitamin D3 in the body. Also found in cod liver oil, raw milk, salmon, tuna [66], [67]

Vitamin E – Naturally occurring vitamin E exists in eight separate and unique forms called tocopherols and tocotrienols, and each form has a different potency or level of activity in the body. Found in amaranth, barley, black rice, Brazil nuts, brown rice, buckwheat bran, cashews, chickpeas, green beans, hemp seed, lentils, macadamia nuts, oats, pecans, pistachios, quinoa, red beans, rice bran, sesame seeds, spelt, walnuts, wheat, wheat bran [68], [69]

Zinc, a mineral found in adzuki beans, amaranth, barley, beets, Brazil nuts, black beans, cashews, chia seeds, flaxseed, hemp seeds, kidney/cannellini beans, lentils, macadamia nuts, oats, pistachio nuts, pumpkin seeds, quinoa, red beans, sesame seeds, soybeans, spelt, wheat, wheat bran [70], [71]

Please note that this is not an exhaustive list, there are hundreds of other anti-inflammatory foods and supplements, but these are some of the best known with the most research.

For more information on other epigenetic factors that reduce breast cancer risk, please see
Part 1 nutrients that can control regulatory genes

Epigenetic Factors to Reduce Breast Cancer Risk – Part 1


Part 2 nutrients that can reduce damage to DNA.

Epigenetic Factors to Reduce Breast Cancer Risk – Part 2


Part 3 nutrients that stop rapid proliferation of cells

Epigenetic Factors to Reduce Breast Cancer Risk – Part 3


and stay tuned for upcoming articles in this 12-part series.

References:

[1] Anti-Inflammatory Agents for Cancer Therapy – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2843097/

[2] Phytochemicals and Cytotoxicity of Launaea procumbens on Human Cancer Cell Lines – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5068119/

[3] Anti-inflammatory potential of alpha-linolenic acid mediated through selective COX inhibition: computational and experimental data – https://www.ncbi.nlm.nih.gov/pubmed/24639012

[4] Bioaccessibility, bioavailability, and anti-inflammatory effects of anthocyanins from purple root vegetables using mono- and co-culture cell models – https://www.ncbi.nlm.nih.gov/pubmed/28691370

[5] Anti-Inflammatory and Anticancer Activities of Taiwanese Purple-Fleshed Sweet Potatoes (Ipomoea batatas L. Lam) Extracts – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4609785/

[6] Apigenin inhibits TNFa/IL-1a-induced CCL2 release through IKBK-epsilon signaling in MDA-MB-231 human breast cancer cells – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5404872/

[7] Apigenin: A dietary flavonoid with diverse anticancer properties – https://www.ncbi.nlm.nih.gov/pubmed/29097249

[8] Synthesis and Identification of Novel Berberine Derivatives as Potent Inhibitors against TNF-a-Induced NF-kB Activation – https://www.ncbi.nlm.nih.gov/pubmed/28749438

[9] Berberis vulgaris and its constituent berberine as antidotes and protective agents against natural or chemical toxicities – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478782/

[10] Beta-Sitosterol: A Promising but Orphan Nutraceutical to Fight Against Cancer – https://www.ncbi.nlm.nih.gov/pubmed/26473555

[11] Beta-Sitosterol, Beta-Sitosterol Glucoside, and a Mixture of Beta-Sitosterol and Beta-Sitosterol Glucoside Modulate the Growth of Estrogen- Responsive Breast Cancer Cells In Vitro and in Ovariectomized Athymic Mice – https://www.ncbi.nlm.nih.gov/pubmed/15113961

[12] Anti-inflammatory effects of betaine on AOM/DSS-induced colon tumorigenesis in ICR male mice – https://www.ncbi.nlm.nih.gov/pubmed/24969167

[13] Betaine reduces the expression of inflammatory adipokines caused by hypoxia in human adipocytes – https://www.ncbi.nlm.nih.gov/pubmed/22424556

[14] Main Isoflavones Found in Dietary Sources as Natural Anti-inflammatory Agents – https://www.ncbi.nlm.nih.gov/pubmed/29141545

[15] Biochanin A attenuates LPS-induced pro-inflammatory responses and inhibits the activation of the MAPK pathway in BV2 microglial cells – https://www.ncbi.nlm.nih.gov/pubmed/25483920

[16] Anti-inflammatory activity of caffeic acid derivatives isolated from the roots of Salvia miltiorrhiza Bunge – https://www.ncbi.nlm.nih.gov/pubmed/29124660

[17] Dietary Intervention by Phytochemicals and Their Role in Modulating Coding and Non-Coding Genes in Cancer – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486001/

[18] Anti-tumor promoting potential of selected spice ingredients with antioxidative and anti-inflammatory activities: a short review – http://www.sciencedirect.com/science/article/pii/S0278691502000376

[19] Capsaicin exhibits anti-inflammatory property by inhibiting IkB-a degradation in LPS-stimulated peritoneal macrophages – http://www.sciencedirect.com/science/article/pii/S0898656802000864

[20] Anti-inflammatory actions of green tea catechins and ligands of peroxisome proliferator-activated receptors – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2517497/

[21] Chlorophyll revisited: anti-inflammatory activities of chlorophyll a and inhibition of expression of TNF-a gene by the same – https://www.ncbi.nlm.nih.gov/pubmed/22038065

[22] Conjugated linoleic acid isomers and cancer – https://www.ncbi.nlm.nih.gov/pubmed/18029471

[23] Downregulation of inflammatory markers by conjugated linoleic acid isomers in human cultured astrocytes – https://www.ncbi.nlm.nih.gov/pubmed/28847225

[24] Conjugated linoleic acid (CLA) modulates prostaglandin E2 (PGE2) signaling in canine mammary cells – https://www.ncbi.nlm.nih.gov/pubmed/16619484

[25] Curcumin inhibits cyclooxygenase-2 transcription in bile acid- and phorbol ester-treated human gastrointestinal epithelial cells – https://www.ncbi.nlm.nih.gov/pubmed/10190560

[26] Curcumin potentiates the potent antitumor activity of ACNU against glioblastoma by suppressing the PI3K/AKT and NF-kB/COX-2 signaling pathways – https://www.ncbi.nlm.nih.gov/pubmed/29180881

[27] Epigenetic diet: impact on the epigenome and cancer – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197720/

[28] Evaluation of the anti-inflammatory effects of ellagic acid – https://www.ncbi.nlm.nih.gov/pubmed/20656257

[29] Anti-inflammatory and antiedematogenic activity of the Ocimum basilicum essential oil and its main compound estragole: In vivo mouse models – https://www.ncbi.nlm.nih.gov/pubmed/27474066

[30] Alkaloids from Piper nigrum Exhibit Antiinflammatory Activity via Activating the Nrf2/HO-1 Pathway – https://www.ncbi.nlm.nih.gov/pubmed/28185326

[31] Studies on the anti-inflammatory and analgesic activity of Cedrus deodara (Roxb.) Loud. wood oil – https://www.ncbi.nlm.nih.gov/pubmed/10350366

[32] Antiinflammatory Activity of Cinnamon (Cinnamomum zeylanicum) Bark Essential Oil in a Human Skin Disease Model – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5518441/

[33] Oral administration of d-limonene controls inflammation in rat colitis and displays anti-inflammatory properties as diet supplementation in humans – https://www.ncbi.nlm.nih.gov/pubmed/23665426

[34] Anti-inflammatory activity of clove (Eugenia caryophyllata) essential oil in human dermal fibroblasts – https://www.ncbi.nlm.nih.gov/pubmed/28407719

[35] Anti-inflammatory activity of oleoresin from Brazilian Copaifera – https://www.ncbi.nlm.nih.gov/pubmed/3352280

[36] A Review of Anti-inflammatory Terpenoids from the Incense Gum Resins Frankincense and Myrrh – https://www.ncbi.nlm.nih.gov/pubmed/28381769

[37] Review of Anti-Inflammatory Herbal Medicines – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877453/

[38] Lavandula angustifolia Mill. Essential Oil Exerts Antibacterial and Anti-Inflammatory Effect in Macrophage Mediated Immune Response to Staphylococcus aureus – https://www.ncbi.nlm.nih.gov/pubmed/26730790

[39] Biological activities of Rosmarinus officinalis L. (rosemary) extract as analyzed in microorganisms and cells – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5685262/

[40] Evaluation of anti-inflammatory activity of ethanolic extract of Cananga odorata Lam in experimental animals – http://www.ijbcp.com/index.php/ijbcp/article/view/926

[41] High dietary fiber intake is associated with decreased inflammation and all-cause mortality in patients with chronic kidney disease – http://www.sciencedirect.com/science/article/pii/S0085253815552903

[42] Effects of dietary fiber intake on inflammation in chronic diseases – http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1679-45082010000200254

[43] Gamma linolenic acid, an antiinflammatory omega-6 fatty acid – https://www.researchgate.net/profile/Rakesh_Kapoor4/publication/6630684_Gamma_Linolenic_Acid_An_Antiinflammatory_Omega-6_Fatty_Acid/links/56df449308aec4b3333b6ecc.pdf

[44] Complementary actions of docosahexaenoic acid and genistein on COX-2, PGE2 and invasiveness in MDA-MB-231 breast cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/17052999

[45] Antioxidants, anti-inflammatory, and antidiabetic effects of the aqueous extracts from Glycine species and its bioactive compounds – https://www.ncbi.nlm.nih.gov/pubmed/28597448

[46] Brassica-Derived Plant Bioactives as Modulators of Chemopreventive and Inflammatory Signaling Pathways – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618539/

[47] Sulforaphane protects against acrolein-induced oxidative stress and inflammatory responses: modulation of Nrf-2 and COX-2 expression – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947616/

[48] STAT3 and NF-kB are common targets for kaempferol-mediated attenuation of COX-2 expression in IL-6-induced macrophages and carrageenan-induced mouse paw edema – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5613220/

[49] Kaempferol Alleviates the Interleukin-1ß-Induced Inflammation in Rat Osteoarthritis Chondrocytes via Suppression of NF-kB – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566200/

[50] Luteolin triggers global changes in the microglial transcriptome leading to a unique anti-inflammatory and neuroprotective phenotype – https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-7-3

[51] Luteolin and chrysin differentially inhibit cyclooxygenase-2 expression and scavenge reactive oxygen species but similarly inhibit prostaglandin-E2 formation in RAW 264.7 cells – https://www.ncbi.nlm.nih.gov/pubmed/16702314

[52] Naringenin: an analgesic and anti-inflammatory citrus flavanone – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354790/

[53] Effect of Citrus Flavonoids, Naringin and Naringenin, on Metabolic Syndrome and Their Mechanisms of Action – http://advances.nutrition.org/content/5/4/404.full

[54] Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology? – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575932/

[55] Health effects of omega-3,6,9 fatty acids: Perilla frutescens is a good example of plant oils – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3167467/

[56] Comparison of the Neuroprotective and Anti-Inflammatory Effects of the Anthocyanin Metabolites, Protocatechuic Acid and 4-Hydroxybenzoic Acid – https://www.hindawi.com/journals/omcl/2017/6297080/

[57] Anti-inflammatory and analgesic activity of protocatechuic acid in rats and mice – https://www.ncbi.nlm.nih.gov/pubmed/21748471

[58] Quercetin attenuates collagen-induced arthritis by restoration of Th17/Treg balance and activation of Heme Oxygenase 1-mediated anti-inflammatory effect -https://www.ncbi.nlm.nih.gov/pubmed/29149703

[59] Quercetin, Inflammation and Immunity – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808895/

[60] Resveratrol Directly Targets COX-2 to Inhibit Carcinogenesis – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2562941/

[61] The inhibitory effect of resveratrol on COX-2 expression in human colorectal cancer: a promising therapeutic strategy – https://www.ncbi.nlm.nih.gov/pubmed/28338176

[62] Gynostemma pentaphyllum saponins attenuate inflammation in vitro and in vivo by inhibition of NF-kB and STAT3 signaling – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675642/

[63] Two new dammarane-type triterpene saponins from Korean red ginseng and their anti-inflammatory effects – https://www.ncbi.nlm.nih.gov/pubmed/29100799

[64] The Role of Selenium in Inflammation and Immunity: From Molecular Mechanisms to Therapeutic Opportunities – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277928/

[65] Selenium regulates cyclooxygenase-2 and extracellular signal-regulated kinase signaling pathways by activating AMP-activated protein kinase in colon cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/17047069

[66] Vitamin D improves inflammatory bowel disease outcomes: Basic science and clinical review – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4009525/

[67] Vitamin D and Breast Cancer – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3267821/

[68] Natural Forms of Vitamin E as Effective Agents for Cancer Prevention and Therapy – https://www.ncbi.nlm.nih.gov/pubmed/29141970

[69] Natural forms of vitamin E: metabolism, antioxidant and anti-inflammatory activities and the role in disease prevention and therapy – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4120831/

[70] Evaluation of Antioxidant Intakes in Relation to Inflammatory Markers Expression Within the Normal Breast Tissue of Breast Cancer Patients – https://www.ncbi.nlm.nih.gov/pubmed/27903840

[71] Zinc is an Antioxidant and Anti-Inflammatory Agent: Its Role in Human Health – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429650/

GET MY BEST TIPS on getting through breast cancer and preventing recurrences by signing up for my free e-newsletters and e-books on the right. You can also “like” me on Facebook (Marnie Clark, Breast Health Coach) to get my inspirational snippets, news and updates. I promise to do my utmost to keep you informed and empowered on your healing journey… and beyond.

Epigenetic Factors to Reduce Breast Cancer Risk – Part 3

Image source: rgbstock.com / Tomislav Alajbeg

Epigenetic Factors To Reduce Breast Cancer Risk – Part 3

In this series of articles, it is my goal to empower you with information about the epigenetic factors that can be used to not only reduce breast cancer risk, but also to help heal yourself from breast cancer if you have had the misfortune of a diagnosis.

For more information on my personal reasons for putting this information together, see Part 1 of the series.

This article, Part 3 in the series, will cover the nutrients that prevent rapid cell proliferation. Proliferation means a rapid increase in the number or amount of something, and in this case it means cancer cells. Their ability to multiply and rapidly grow is one of the hallmarks of cancer. Many anti-cancer drugs such as chemotherapy target this very thing. Unfortunately, however, these drugs come at a price because they don’t just target rapidly growing cancer cells, they target every cell that is rapidly growing. The beauty of epigenetic nutrients is that they don’t target healthy cells that are rapidly growing – they leave them alone.

PART 3 – NUTRIENTS THAT CAN PREVENT RAPID CELL PROLIFERATION

The nutrients listed below are capable of blocking the continuous multiplication of the cellular replication cycle, thus stopping or slowing cancer cell growth. Few of them have been included in human trials, so we don’t have exact doses, but we can certainly include them as part of a healthy anti-cancer diet.

1. Alpha linolenic acid, derived from chia, flaxseed, hemp seeds, pecans, pistachio nuts, pumpkin seeds, walnuts [1]
2. Apigenin, derived from celery, parsley, onions, grapefruit, oranges  [2], [3]
3. Berberine, derived from goldenseal, barberry, Oregon grape, Huang bai, tree turmeric [4], [5]
4. Beta-sitosterol, derived from rice bran, pistachio nuts, walnuts, almonds, pecans, pumpkin seeds, sesame seeds, sunflower seeds [6]
5. Caffeic acid, derived from adzuki beans, apples, apicots, buckwheat bran, brown rice, chia seeds, chickpeas, coffee, hazelnuts, lentils, sunflower seeds [7]. Caffeic acid also reduces the growth of cancer stem cells [8].
6. Catechin and epicatechin, derived from adzuki beans, almonds, apricots, bilberries, chickpeas, green beans, green tea, lentils, pecans [9] [10].
7. Chlorophyll, derived from all green plants, pumpkin seeds, fresh herbs, blue-green algae, sprouts, wheatgrass, matcha tea, sea weed, grapes, green beans [11] .
8. Curcumin, derived from turmeric [12].
9. Delphinidin, derived from black beans, blackcurrants  [13].
10. Eicosapentaenoic acid (EPA), derived from chia seeds, flaxseed, hemp seeds [14].
11. Ellagic acid, derived from apples, raspberries, black raspberries, blackberries, Brazil nuts, pecans, walnuts, pomegranates, wild strawberries, cranberries [15].
12. Enterolactone, derived from steel cut oats, flaxseed [16].
13. Epigallocatechin gallate (EGCG), derived from green tea [17].
14. Eugenol, derived from cinnamon, clove [18], [19].
15. Ferulic acid, derived from apricots, grapes, rice bran, brown rice, black beans, chickpeas, dong quai, hazelnuts, sesame seeds [20], [21]. 16. Formononetin, derived from red clover  [22].
17. Jasmonic acid, derived from apples, chickpeas, jasmine essential oil  [23].
18. Juglone, derived from walnuts [24].
19. Kaempferol, derived from black beans, chickpeas, chia seeds, green beans, lentils [25].
20. Lectins, derived from Anasazi beans and other beans, mushrooms [26].
21. Lutein, derived from kale, broccoli, pecans, pistachio nuts, pumpkin seeds, walnuts, green beans  [27].
22. Lycopene, derived from apricots, tomatoes [28], [29].
23. Medicinal Mushrooms – many medicinal mushrooms (such as reishi, turkey tail, shiitake, etc) have anti-proliferatory properties, see my article  Medicinal Mushrooms – Fungi That Fight Cancer Cells to see which ones.
24. Melatonin, derived from black rice, walnuts, barley, bananas [30].
25. Momilactone B, derived from brown rice [31].
26. Protocatechuic acid, derived from acai, adzuki beans, apples, avocados, brown rice, hazelnuts, pistachio nuts, bilberries, blackberries, blueberries, buckwheat, cauliflower, dates, eggplant, garlic, kiwi, lentils, mango, mangosteen, mulberries, olive oil, olives, pears, raspberries, red onion, strawberries [32].
27. Pterostilbene, derived from blueberries, cranberries, lingonberries, grapes [33].
28. Quercetin, derived from adzuki beans, apples, apricots, bilberries, black beans, chickpeas, chia seeds, green beans, lentils [34].
29. Saponins, derived from amaranth, asparagus, black beans, green beans, sunflower seeds, soybeans, oats, spinach, chickpeas, quinoa, tomatoes, Panax ginseng  [35], [36].
30. Selenium, derived from wheat germ, wheat bran, Brazil nuts, pecans, brewer’s yeast, broccoli, brown rice, chicken, garlic, kelp, lentils, liver, molasses, onions, salmon, seafood, vegetables, whole grains, chickpeas, pistachio nuts, pumpkin seeds, sunflower seeds, walnuts [37].
31. Sesamin and sesamol, derived from sesame seeds [38].
32. Sinapic acid, derived from brown rice, citrus fruits, lentils, sunflower seeds [39].
33. Sulforaphane, derived from cruciferous vegetables [40].
34. Syringic acid, derived from walnuts, chard, molasses, millet [41].
35. Triticuside A, derived from wheat bran [42].
36. Vitamin E, derived from black rice, brown rice, cashews, chickpeas, lentils, pecans, pistachio nuts, sesame seeds, walnuts, green beans, rice bran, wheat bran [43].

Please note that this is not an exhaustive list, there are likely many other substances that will prevent rapid cell proliferation. But this will definitely get you started in the right direction!

For more information on other epigenetic factors that reduce breast cancer risk, please see:
Part 1 nutrients that can control regulatory genes
Part 2 nutrients that can reduce damage to DNA
and stay tuned for upcoming articles in this 12-part series.

References:

[1] a-Linolenic Acid Reduces Growth of Both Triple Negative and Luminal Breast Cancer Cells in High and Low Estrogen Environments – https://www.ncbi.nlm.nih.gov/pubmed/26134471

[2] Exposure of breast cancer cells to a subcytotoxic dose of apigenin causes growth inhibition, oxidative stress, and hypophosphorylation of Akt – https://www.ncbi.nlm.nih.gov/pubmed/25019465

[3] Induction of caspase-dependent extrinsic apoptosis by apigenin through inhibition of signal transducer and activator of transcription 3 (STAT3) signalling in HER2-overexpressing BT-474 breast cancer cells – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4708008/

[4] Berberine Enhances Chemosensitivity and Induces Apoptosis Through Dose-orchestrated AMPK Signaling in Breast Cancer – https://www.ncbi.nlm.nih.gov/pubmed/28775788

[5] Interaction of Herbal Compounds with Biological Targets: A Case Study with Berberine – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504405/

[6] Beta-Sitosterol, Beta-Sitosterol Glucoside, and a Mixture of Beta-Sitosterol and Beta-Sitosterol Glucoside Modulate the Growth of Estrogen- Responsive Breast Cancer Cells In Vitro and in Ovariectomized Athymic Mice – https://www.ncbi.nlm.nih.gov/pubmed/15113961

[7] Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC400651

[8] Blockage of TGFß-SMAD2 by demethylation-activated miR-148a is involved in caffeic acid-induced inhibition of cancer stem cell-like properties in vitro and in vivo – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4475776/

[9] Breast cancer chemopreventive and chemotherapeutic effects of Camellia Sinensis (green tea): an updated review – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410915

[10] Suppressive Effects of Tea Catechins on Breast Cancer – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997373/

[11] The chlorophyllin-induced cell cycle arrest and apoptosis in human breast cancer MCF-7 cells is associated with ERK deactivation and Cyclin D1 depletion – https://www.ncbi.nlm.nih.gov/pubmed/16142413

[12] Curcumin Suppresses Proliferation and Migration of MDA-MB-231 Breast Cancer Cells through Autophagy-Dependent Akt Degradation – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4708990/

[13] Delphinidin inhibits cell proliferation and invasion via modulation of Met receptor phosphorylation – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989819/

[14] Eicosapentaenoic acid suppresses cell proliferation in MCF-7 human breast cancer xenografts in nude rats via a pertussis toxin-sensitive signal transduction pathway – https://www.ncbi.nlm.nih.gov/pubmed/16140887

[15] Ellagic acid induces cell cycle arrest and apoptosis through TGF-ß/Smad3 signaling pathway in human breast cancer MCF-7 cells – https://www.ncbi.nlm.nih.gov/pubmed/25647396

[16] Estrogen-induced angiogenic factors derived from stromal and cancer cells are differently regulated by enterolactone and genistein in human breast cancer in vivo – https://www.ncbi.nlm.nih.gov/pubmed/19924815

[17] EGFR inhibition by (-)-epigallocatechin-3-gallate and IIF treatments reduces breast cancer cell invasion – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5434892/

[18] Eugenol Triggers Apoptosis in Breast Cancer Cells Through E2F1/survivin. Down-regulation – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931838/

[19] Chemosensitivity of MCF-7 cells to eugenol: release of cytochrome-c and lactate dehydrogenase – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341120/

[20] Lipophilic caffeic and ferulic acid derivatives presenting cytotoxicity against human breast cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/21504213

[21] Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC400651/

[22] Formononetin induces cell cycle arrest of human breast cancer cells via IGF1/PI3K/Akt pathways in vitro and in vivo – https://www.ncbi.nlm.nih.gov/pubmed/21932171/

[23] Plant stress hormones suppress the proliferation and induce apoptosis in human cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/11960340

[24] Effect of Pin1 inhibitor juglone on proliferation, migration and angiogenic ability of breast cancer cell line MCF7Adr – https://www.ncbi.nlm.nih.gov/pubmed/26223922

[25] Kaempferol, a Flavonoid Compound from Gynura Medica Induced Apoptosis and Growth Inhibition in MCF-7 Breast Cancer Cell – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566146/

[26] A Hemagglutinin from Northeast Red Beans with Immunomodulatory Activity and Anti-proliferative and Apoptosis-inducing Activities Toward Tumor Cells – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300056/

[27] Selective Carotenoid Growth Inhibition in Breast Cancer: Independence of Hormonal Sensitivity – http://www.fasebj.org/content/29/1_Supplement/32.3.short

[28] Selective inhibition of cell proliferation by lycopene in MCF-7 breast cancer cells in vitro: a proteomic analysis – https://www.ncbi.nlm.nih.gov/pubmed/22718574

[29] Selective Carotenoid Growth Inhibition in Breast Cancer: Independence of Hormonal Sensitivity – http://www.fasebj.org/content/29/1_Supplement/32.3.short

[30] Melatonin receptors, melatonin metabolizing enzymes and cyclin D1 in human breast cancer – https://www.ncbi.nlm.nih.gov/pubmed/21385053

[31] Enhancement of hypoxia-induced apoptosis of human breast cancer cells via STAT5b by momilactone B – https://www.ncbi.nlm.nih.gov/pubmed/18695876

[32] Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC400651/

[33] Pterostilbene simultaneously induces apoptosis, cell cycle arrest and cyto-protective autophagy in breast cancer cells – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276376/

[34] Quercetin induces apoptosis and necroptosis in MCF-7 breast cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/28814095

[35]  Saponins as cytotoxic agents: a review – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928447/

[36] Anti-proliferating effects of ginsenoside Rh2 on MCF-7 human breast cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/10200336

[37] Selenium and Breast Cancer Risk: Focus on Cellular and Molecular Mechanisms http://www.sciencedirect.com/science/article/pii/S0065230X17300374 /

[38] Effect of sesamin on apoptosis and cell cycle arrest in human breast cancer mcf-7 cells – https://www.ncbi.nlm.nih.gov/pubmed/25987037

[39] Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC400651/

[40] Sulforaphane–a possible agent in prevention and therapy of cancer – https://www.ncbi.nlm.nih.gov/pubmed/21160094/

[41] Phenolic and carotenoid profiles and antiproliferative activity of foxtail millet – https://www.ncbi.nlm.nih.gov/pubmed/25529711

[42] Triticuside A, a Dietary Flavonoid, Inhibits Proliferation of Human Breast Cancer Cells via Inducing Apoptosis – https://www.ncbi.nlm.nih.gov/pubmed/23909734

[43]  Inhibitory Effects of Gamma- and Delta-Tocopherols on Estrogen- Stimulated Breast Cancer In Vitro and In Vivo – https://www.ncbi.nlm.nih.gov/pubmed/28096236 /

GET MY BEST TIPS on getting through breast cancer and preventing recurrences by signing up for my free e-newsletters and e-books on the right. You can also “like” me on Facebook (Marnie Clark, Breast Health Coach) to get my inspirational snippets, news and updates. I promise to do my utmost to keep you informed and empowered on your healing journey… and beyond.

Epigenetic Factors to Reduce Breast Cancer Risk – Part 2

Image Source: rgbstock.com / Tomislav Alajbeg

Epigenetic Factors to Reduce Breast Cancer Risk – Part 2

One of the most fascinating areas of breast cancer research has to be the field of epigenetics and how genes can be expressed differently by using external factors, all without altering the DNA structure of those genes. At first ridiculed by the scientific community, epigenetics is now one of the fastest growing fields of science.

Continuing on from Part 1 in my series of epigenetic factors to reduce breast cancer risk, this article will cover the nutrients that help to prevent damage to DNA.

PART 2 – NUTRIENTS THAT CAN PREVENT DAMAGE TO DNA

As with many other types of cancer, breast cancer generally begins with something happening to alter the DNA function or structure of just one cell. This can trigger that cell to become malignant and a tumor to form, and that process can take months or years, depending upon hundreds of different factors. Other things that are happening when the tumor is forming (to put it in simplest terms) is that a tumor suppressor gene has become silenced or a tumor promoter gene has been activated and allows unchecked cell replication.

The good news is that many nutrients have the ability to prevent and protect against DNA damage. Here is the list of the best 20.

The Top 20 Nutrients that Prevent DNA Damage

1. Curcumin, derived from turmeric [1], [2], [3], [48]

2. Epigallocatechin gallate (EGCG), derived from green tea [4], [5], [6], [47], [48]

3. Coenzyme Q10 [7], [8], [9]

4. Di-indolyl-methane (DIM) [10], [11], [48]

5. Coffee [12], [13]

6. N-acetylcysteine (NAC) [14], [15], [23]

7. Melatonin, a natural hormone [16], [17]

8. Lycopene, derived from tomato, watermelon, guava, papaya [18], [19]

9. Pomegranate [20], [21], [22]

10. Resveratrol, derived from grapes, blueberries [23], [24], [25], [48]

11. Selenium [26], [27], [48]

12. Silibinin and silymarin, derived from milk thistle [28], [29], [30], [31], [53]

13. Sulforaphane, derived from cruciferous vegetables [32], [33], [34], [48]

14. Tocotrienols, derived from vitamin E [35], [36], [37], [38]

15. Genistein and diadzein, derived from soybeans [39], [40], [41], [48]

16. Garlic and onions [42], [43], [44], [45], [48]

17. Quercetin [46], [47], [48]

18. Luteolin, derived from celery, oregano, thyme, chili peppers [47], [49], [50], [52]

19. Apigenin, derived from celery, parsley, onions, grapefruit, oranges, chamomile tea [47], [51], [52]

20. Chrysin, derived from passionflower [47], [52], [53]

Mind-Body Interventions Also Play A Role in DNA Repair

A recent study [54] carried out by scientists from Coventry University In the UK and Radboud University in the Netherlands demonstrated that mind-body interventions can have an enormous impact on DNA repair. The study analyzed more than 10 years worth of research studies on how mind-body interventions impact DNA and they found that things like yoga, meditation and Tai Chi can actually reverse the deleterious effects that things like stress and other factors might otherwise have on DNA.

The researchers found that people who regularly practice mind-body interventions enjoy a reduction in the production of inflammatory markers. This in turn leads to a reduction and reversal of pro-inflammatory gene expression, thus lowering  the risk of inflammation-related conditions. And as we know, breast cancer is definitely an inflammatory condition. Have a look at the study, it’s reference #54 below.

While this is not an exhaustive list, it will certainly give you a great idea how many natural substances help to protect DNA and reduce breast cancer risk. For more information on the subject of epigenetic factors that reduce breast cancer risk, please see Part 1 of this series of articles which discussed nutrients that can control regulator genes and stay tuned for upcoming articles in this 12-part series.

References:

[1] Curcumin downregulates the inflammatory cytokines CXCL1 and -2 in breast cancer cells via NfkappaB – https://www.ncbi.nlm.nih.gov/pubmed/17999991

[2] Expression profiles of apoptotic genes induced by curcumin in human breast cancer and mammary epithelial cell lines – https://www.ncbi.nlm.nih.gov/pubmed/16101141

[3] Curcumin inhibits breast cancer stem cell migration by amplifying the E-cadherin/ß-catenin negative feedback loop – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445824/

[4] Green tea polyphenol and epigallocatechin gallate induce apoptosis and inhibit invasion in human breast cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/18059161

[5] Anticancer effects and molecular mechanisms of epigallocatechin-3-gallate – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481703/

[6] Mechanism of EGCG promoting apoptosis of MCF-7 cell line in human breast cancer – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5588052/

[7] Augmented efficacy of tamoxifen in rat breast tumorigenesis when gavaged along with riboflavin, niacin, and CoQ10: effects on lipid peroxidation and antioxidants in mitochondria – https://www.ncbi.nlm.nih.gov/pubmed/15766922

[8] Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients – https://www.ncbi.nlm.nih.gov/pubmed/10936586

[9] Exogenous coenzyme Q10 modulates MMP-2 activity in MCF-7 cell line as a breast cancer cellular model – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3004807/

[10] Inhibitory effects of 3,3′-diindolylmethane on epithelial-mesenchymal transition induced by endocrine disrupting chemicals in cellular and xenograft mouse models of breast cancer – https://www.ncbi.nlm.nih.gov/pubmed/28844962

[11] Chemopreventive properties of 3,3′-diindolylmethane in breast cancer: evidence from experimental and human studies – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5059820/

[12] Coffee consumption rapidly reduces background DNA strand breaks in healthy humans: Results of a short-term repeated uptake intervention study – https://www.ncbi.nlm.nih.gov/pubmed/26632023

[13] Inhibition of DNA methylation by caffeic acid and chlorogenic acid, two common catechol-containing coffee polyphenols – https://www.ncbi.nlm.nih.gov/pubmed/16081510

[14] N-acetyl-cysteine promotes angiostatin production and vascular collapse in an orthotopic model of breast cancer – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1615662/

[15] N-Acetyl-L-cysteine protects thyroid cells against DNA damage induced by external and internal irradiation – https://www.ncbi.nlm.nih.gov/pubmed/28871381

[16] Melatonin modulates aromatase activity and expression in endothelial cells – https://www.ncbi.nlm.nih.gov/pubmed/23450505

[17] Melatonin modulates aromatase activity in MCF-7 human breast cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/15683469

[18] In vitro effects and mechanisms of lycopene in MCF-7 human breast cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/28407181

[19] Lycopene acts through inhibition of IkB kinase to suppress NF-kB signaling in human prostate and breast cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/26779636

[20] The antioxidant potency of Punica granatum L. Fruit peel reduces cell proliferation and induces apoptosis on breast cancer – https://www.ncbi.nlm.nih.gov/pubmed/21861726

[21] Pomegranate Fruit as a Rich Source of Biologically Active Compounds – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4000966/

[22] Antiproliferative effects of pomegranate extract in MCF-7 breast cancer cells are associated with reduced DNA repair gene expression and induction of double strand breaks – https://www.ncbi.nlm.nih.gov/pubmed/23359482

[23] Resveratrol and N-acetylcysteine block the cancer-initiating step in MCF-10F cells – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425208/

[24] Resveratrol promotes MICA/B expression and natural killer cell lysis of breast cancer cells by suppressing c-Myc/miR-17 pathway – https://www.ncbi.nlm.nih.gov/pubmed/29029468

[25] Antioxidant activities of novel resveratrol analogs in breast cancer – https://www.ncbi.nlm.nih.gov/pubmed/28960787

[26] Dietary Supplementation with Methylseleninic Acid Inhibits Mammary Tumorigenesis and Metastasis in Male MMTV-PyMT Mice – https://www.ncbi.nlm.nih.gov/pubmed/29032404

[27] Selenium modifies the osteoblast inflammatory stress response to bone metastatic breast cancer – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2791325/

[28] Silibinin suppresses EGFR ligand-induced CD44 expression through inhibition of EGFR activity in breast cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/22110198

[29] Silibinin prevents TPA-induced MMP-9 expression by down-regulation of COX-2 in human breast cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/19715751

[30] Silibinin inhibits translation initiation: implications for anticancer therapy – https://www.ncbi.nlm.nih.gov/pubmed/19509268

[31] Silibinin induces protective superoxide generation in human breast cancer MCF-7 cells – https://www.ncbi.nlm.nih.gov/pubmed/19968587

[31] Anticarcinogenic effect of a flavonoid antioxidant, silymarin, in human breast cancer cells MDA-MB 468: induction of G1 arrest through an increase in Cip1/p21 concomitant with a decrease in kinase activity of cyclin-dependent kinases and associated cyclins – https://www.ncbi.nlm.nih.gov/pubmed/9563902

[32] Efficacy of sulforaphane is mediated by p38 MAP kinase and caspase-7 activations in ER-positive and COX-2-expressed human breast cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/18090122

[33] Sulforaphane-Induced Cell Cycle Arrest and Senescence are accompanied by DNA Hypomethylation and Changes in microRNA Profile in Breast Cancer Cells – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596436/

[34] A Novel Combination of Withaferin A and Sulforaphane Inhibits Epigenetic Machinery, Cellular Viability and Induces Apoptosis of Breast Cancer Cells – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455001/

[35] Gamma-tocotrienol controls proliferation, modulates expression of cell cycle regulatory proteins and up-regulates quinone reductase NQO2 in MCF-7 breast cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/20683025

[36] Role of Rac1/WAVE2 Signaling in Mediating the Inhibitory Effects of Gamma-Tocotrienol on Mammary Cancer Cell Migration and Invasion – https://www.ncbi.nlm.nih.gov/pubmed/27904039

[37] Tocotrienols and breast cancer: the evidence to date – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250526/

[38] Gamma-tocotrienol induced apoptosis is associated with unfolded protein response in human breast cancer cells – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123668/

[39] DNA Methylation Targets Influenced by Bisphenol A and/or Genistein Are Associated with Survival Outcomes in Breast Cancer Patients – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5448018/

[40] The Role of Soy Phytoestrogens on Genetic and Epigenetic Mechanisms of Prostate Cancer – https://www.ncbi.nlm.nih.gov/pubmed/26298461

[41] Multi-targeted Therapy of Cancer by Genistein – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2575691/

[42] 2-Methylpyridine-1-ium-1-sulfonate from Allium hirtifolium: An anti-angiogenic compound which inhibits growth of MCF-7 and MDA-MB-231 cells through cell cycle arrest and apoptosis induction – https://www.ncbi.nlm.nih.gov/pubmed/28624423

[43] In vitro Antiproliferative and Apoptosis Inducing Effect of Allium atroviolaceum Bulb Extract on Breast, Cervical, and Liver Cancer Cells – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5281556/

[44] Diallyl trisulfide, a chemopreventive agent from Allium vegetables, inhibits alpha-secretases in breast cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/28161636

[45] The Effects of Allicin, a Reactive Sulfur Species from Garlic, on a Selection of Mammalian Cell Lines – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384165/

[46] Quercetin exerts synergetic anti-cancer activity with 10-hydroxy camptothecin – https://www.ncbi.nlm.nih.gov/pubmed/28822757

[47] Plant flavonoids in cancer chemoprevention: role in genome stability – https://www.ncbi.nlm.nih.gov/pubmed/27951449

[48] Cancer Chemoprotection Through Nutrient-mediated Histone Modifications – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012963/

[49] Luteolin inhibits lung metastasis, cell migration, and viability of triple-negative breast cancer cells – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5207335/

[50] Luteolin suppresses the metastasis of triple-negative breast cancer by reversing epithelial-to-mesenchymal transition via downregulation of ß-catenin expression – https://www.ncbi.nlm.nih.gov/pubmed/27959422

[51] Inhibition of MDA-MB-231 breast cancer cell proliferation and tumor growth by apigenin through induction of G2/M arrest and histone H3 acetylation-mediated p21WAF1/CIP1 expression – https://www.ncbi.nlm.nih.gov/pubmed/26872304

[52] Dietary Flavones as Dual Inhibitors of DNA Methyltransferases and Histone Methyltransferases – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033486/

[53] Synergistic Anticancer Effects of Silibinin and Chrysin in T47D Breast Cancer Cells – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555536/

[54] What Is the Molecular Signature of Mind–Body Interventions? A Systematic Review of Gene Expression Changes Induced by Meditation and Related Practices – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472657/

DISCLAIMER: The purpose of this article is to provide information. It should not be interpreted as medical advice, and is not intended to diagnose, treat or cure any medical condition, or to be a substitute for advice from your health care professional. If you have breast cancer, it is important that you work closely with a health care professional to properly treat your condition and monitor your progress.

GET MY BEST TIPS on getting through breast cancer and preventing recurrences by signing up for my free e-newsletters and e-books on the right. You can also “like” me on Facebook (Marnie Clark, Breast Health Coach) to get my inspirational snippets, news and updates. I promise to do my utmost to keep you informed and empowered on your healing journey… and beyond.

Epigenetic Factors to Reduce Breast Cancer Risk – Part 1

Epigenetic Factors to Reduce Breast Cancer Risk – Part 1

Epigenetic factors to reduce breast cancer risk has been a particular interest of mine ever since I found out that I had breast cancer in 2004. I have studied everything I could lay my hands on with reference to epigenetic factors. The word means “above genetics” and is the science of how genes can be expressed differently using external factors without changing the DNA structure of those genes.

The reason epigenetics interests me so greatly is because I lost both my mother and my grandmother to breast cancer. When I was subsequently diagnosed with breast cancer myself, I was quite concerned about the so-called genetic aspect of this disease. I spoke about this with a friend of mine and I can remember saying to her “What if everything I’m doing to get well and stay well turns out not to be enough if I’m genetically predisposed to breast cancer?” Her response was to introduce me to a scientist named Bruce Lipton and a whole new way of thinking. Dr Lipton’s book “The Biology of Belief” helped me to understand that we do not have to be slaves to our genes. The book introduced me to the  concept of epigenetic factors which can influence the expression of genes.

I learned that nutrition, thoughts, exercise and quite a few other factors can influence our genes in a very powerful way. What an immensely liberating thought – that we mere humans can play a huge role in turning off the very genes that might otherwise predispose us to breast cancer.

In a series of articles, I will be sharing some of the epigenetic nutrients that provide us with the ability to alter genetic expression, thus possibly preventing or reversing breast cancer. From my best count, here are the best 11 ways they do this (and one article will be devoted to each subject):

Epigenetic nutrients can:

1. Control regulatory genes
2. Prevent damage to DNA
3. Prevent rapid cell proliferation
4. Ease or prevent cancer-promoting inflammation
5. Change malignant cells into healthy cells
6. Restore receptors on cells
7. Inhibit excess estrogen production
8. Trigger cancer cell death (apoptosis)
9. Block growth factors
10. Block angiogenesis
11. Prevent metastasis

PART 1 – NUTRIENTS THAT CAN CONTROL REGULATORY GENES

Through genetic testing, we know that there are a number of gene defects that can predispose a person to certain diseases, including breast cancer. There are quite literally hundreds of ways genes can be influenced to control, slow or stop breast cancer growth. Any of these genes, when faulty, damaged or disrupted, can put us at a higher risk for breast cancer. Fortunately, there are a number of nutrients that have epigenetic targets in cancer cells and they block these processes, and can help to prevent carcinogenesis (formation of cancer cells).

Here are but a few of the most-studied genes involved with breast cancer:

MTHFR

The MTHFR gene plays a critical role in DNA methylation. This is a much-studied and ever-expanding subject, especially for breast cancer patients. According to 2012 research done at the University of Mississippi, a number of genes become abnormally methylated in breast cancer patients. [1] Methylation involves the addition or removal of a methyl group (CH3) to a substance so that it can metabolized. Methylation takes place daily inside cells, millions of times,  and requires the presence of enzymes known as DNA methyltransferases (DNMTs) to catalyze (cause or accelerate) the process.

For example, methylation is required to convert the neurotransmitter serotonin into melatonin. Methylation is involved in converting stronger estrogens into less aggressive estrogens and that is one of the reasons it is included in this discussion. MTHFR working properly means you can break down circulating estrogen and excrete it, otherwise it can build up to dangerously high levels and this increases breast cancer risk. Hypermethylation is known to be associated with estrogen receptor-positive breast cancer. [2]

The problem isn’t just with estrogen, however. MTHFR also provides the directions to produce an enzyme called methylene tetrahydrofolate reductase, which converts inactive folate (vitamin B9) to its active form, levomefolic acid, to enable cells to utilize it. An inability to convert folate into levomefolic acid affects many metabolic processes in the body. Active folate is essential for healthy cell division, DNA synthesis and repair, heart health, good vision, brain development, memory and mood, and so much more.

Helpful Nutrients:

Epigallocatechin-3-gallate – EGCG – found in green tea [3]
Curcumin  – from turmeric [4]
Genistein – from soy [5]
Lycopene – from tomatoes and apricots [5]
Resveratrol [6]
Caffeic acid – found in apples, apicots, buckwheat bran, coffee, chia seeds [7]
Chlorogenic acid – found in apples, tomatoes, black beans, almonds, coffee beans, chia seeds [7]

BRCA1, BRCA2

Much-studied genes, BRCA1 and BRCA2 stand for breast cancer type 1 and type 2 susceptibility proteins. They provide instructions for the creation of proteins that repair damaged DNA and act as tumor suppressors. Having a mutated BRCA1/2 gene has been shown to put a person at a higher risk for breast cancer, ovarian and some other cancers. It is estimated that around 10% of breast cancer cases are caused by mutations in these genes. DNA methylation can be involved here too – a 2014 Chinese study investigating the regulation of DNMT1 (discussed above) in BRCA1-mutated breast cancer found that a transcription factor known as E2F1 was hypermethylated. Another key factor is a process known as histone deacetylation. Without getting into huge detail requiring a chemistry degree to understand it, acetylation of histones involves DNA binding proteins, activation of gene transcription and other cellular functions.  [8] Fortunately, there are a good many nutrients that can play a protective role for those with BRCA1/2 mutations:

Helpful Nutrients:

Genestein – from soy [9]
Epigallocatechin-3-gallate – EGCG, from green tea [9]
Soy foods [10]
Sulforaphane – from broccoli sprouts, cruciferous vegetables [11]
Garlic [11]
Caffeic acid – found in apples, apicots, buckwheat bran, coffee, chia seeds [7]
Chlorogenic acid – found in apples, tomatoes, black beans, almonds, coffee beans, chia seeds [7]
Resveratrol [12]
Vitamin D3 [13]

Special note for BRCA1/2 mutation carriers – when taking B-vitamins, carriers of the BRCA1/2 mutation would be well advised to consult a functional medicine doctor or integrative oncologist specifically trained to deal with this genetic mutation, because there are conflicting studies on the helpfulness of B vitamins for carriers of this mutation. One study reported that high folate levels were associated with an increased risk of breast cancer for BRCA1/2 mutation carriers [14] while another study indicated high folate levels were protective. [15]

Remember too that physical activity has also been found to be associated with a reduction in risk of breast cancer for those with BRCA1/2 mutations. [16]

P53

P53 is a tumor suppressor gene, regulating cell division by keeping cells from proliferating (growing and dividing too fast) or in an uncontrolled way. So you want this one to be working because when P53 is faulty, there is seen to be an associated increase in cancer risk. P53 is considered to be one of the most frequently mutated genes leading to cancer development.

Helpful Nutrients:

Quercetin [17]
Zinc [18]
Apigenin – found in celery, parsley, onions, grapefruit, oranges, chamomile tea [19]
Vitamin D3 [20]
Arenobufagin – isolated from Chan Su, a Traditional Chinese Medicine herb, aka Venenum Bufonis [21] (please do work with a TCM doctor when using this)
Berberine – found in goldenseal, barberry [22]

EZH2

EZH2 is a gene that has been shown in research to be a marker for more aggressive breast cancer. One study indicated “Aberrant expression of EZH2 has been associated with metastasis and poor prognosis in cancer patients.” [23]

Helpful Nutrients:

Omega 3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid) [23]
Ginsenoside RH2 – from Korean red ginseng [24]
Epigallocatechin-3-gallate (EGCG) – from green tea [25]
Curcumin [26]
Sulforaphane [27]
Berberine [28]
Tanshindiol – from the Traditional Chinese Medicine herb, Danshen, or Salvia miltiorrhiza [29]
Melatonin [30]

This is by no means an exhaustive list of regulatory genes, nor the nutrients that help to influence them. The purpose of this article is merely to inform you of the ones I am aware of that do exist and as I find more, I will add them to this lists. As you look through these lists of epigenetic nutrients, you begin to notice the repetition of a few, right? I think it’s pretty clear that those are the ones to focus upon and add to your daily protocols.

References:

[1] Epigenetic events associated with breast cancer and their prevention by dietary components targeting the epigenome – https://www.ncbi.nlm.nih.gov/pubmed/21992498

[2] DNA methylation and hormone receptor status in breast cancer – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754852/

[3] Suppressive Effects of Tea Catechins on Breast Cancer – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997373/

[4] Epigenetic diet: impact on the epigenome and cancer – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197720/

[5] Modulation of gene methylation by genistein or lycopene in breast cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/18181168

[6] Trans-resveratrol alters mammary promoter hypermethylation in women at increased risk for breast cancer – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392022/

[7] Inhibition of DNA methylation by caffeic acid and chlorogenic acid, two common catechol-containing coffee polyphenols – https://www.ncbi.nlm.nih.gov/pubmed/16081510

[8] Regulation of DNA methyltransferase 1 transcription in BRCA1-mutated breast cancer: a novel crosstalk between E2F1 motif hypermethylation and loss of histone H3 lysine 9 acetylation – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3936805/

[9] Reversal Effects of Genistein and (-)-Epigallocatechin-3-Gallate on Repression of BRCA-1 Expression in Human Breast Cancer Cells with Activated AhR – http://www.fasebj.org/content/30/1_Supplement/42.6.short

[10] Dietary intake and breast cancer among carriers and noncarriers of BRCA mutations in the Korean Hereditary Breast Cancer Study – http://ajcn.nutrition.org/content/early/2013/10/23/ajcn.112.057760.abstract

[11] Modulation of Histone Deacetylase Activity by Dietary Isothiocyanates and Allyl Sulfides: Studies with Sulforaphane and Garlic Organosulfur Compounds – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701665/

[12] Acetylated STAT3 is crucial for methylation of tumor-suppressor gene promoters and inhibition by resveratrol results in demethylation – http://www.pnas.org/content/109/20/7765

[13] Cooperation between BRCA1 and vitamin D is critical for histone acetylation of the p21waf1 promoter and for growth inhibition of breast cancer cells and cancer stem-like cells – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322975/

[14] Plasma folate, vitamin B-6, and vitamin B-12 and breast cancer risk in BRCA1- and BRCA2-mutation carriers: a prospective study – http://ajcn.nutrition.org/content/early/2016/07/26/ajcn.116.133470

[15] The effects of plasma folate and other B vitamins on breast cancer risk in BRCA1 and BRCA2 mutation carriers – http://cancerres.aacrjournals.org/content/75/15_Supplement/LB-185

[16] Effects of lifestyle and diet as modifiers of risk of breast cancer (BC) in BRCA1 and BRCA2 carriers – http://ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.1505

[17] Anticarcinogenic action of quercetin by downregulation of phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) via induction of p53 in hepatocellular carcinoma (HepG2) cell line – https://www.ncbi.nlm.nih.gov/pubmed/26311153

[18] Metalloregulation of the tumor suppressor protein p53: zinc mediates the renaturation of p53 after exposure to metal chelators in vitro and in intact cells – http://www.nature.com/onc/journal/v19/n46/full/1203907a.html

[19] Evidence for activation of mutated p53 by apigenin in human pancreatic cancer – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277744/

[20] 1,25-Dihydroxyvitamin D3 regulates T lymphocyte proliferation through activation of P53 and inhibition of ERK1/2 signaling pathway in children with Kawasaki disease – https://www.ncbi.nlm.nih.gov/pubmed/28925469

[21] Arenobufagin Induces Apoptotic Cell Death in Human Non-Small-Cell Lung Cancer Cells via the Noxa-Related Pathway – https://www.ncbi.nlm.nih.gov/pubmed/28892004

[22] Berberine Enhances Chemosensitivity and Induces Apoptosis Through Dose-orchestrated AMPK Signaling in Breast Cancer – https://www.ncbi.nlm.nih.gov/pubmed/28775788

[23] Dietary omega-3 polyunsaturated fatty acids suppress expression of EZH2 in breast cancer cells – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2832544/

[24] 20(S)-Ginsenoside Rh2 suppresses proliferation and migration of hepatocellular carcinoma cells by targeting EZH2 to regulate CDKN2A-2B gene cluster transcription – https://www.ncbi.nlm.nih.gov/pubmed/28928088

[25] (-)-Epigallocatechin-3-gallate and EZH2 inhibitor GSK343 have similar inhibitory effects and mechanisms of action on colorectal cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/28925507

[26] Effect and mechanism of curcumin on EZH2 – miR-101 regulatory feedback loop in multiple myeloma – https://www.ncbi.nlm.nih.gov/pubmed/28322158

[27] The Ezh2 Polycomb Group Protein Drives an Aggressive Phenotype in Melanoma Cancer Stem Cells and is a Target of Diet Derived Sulforaphane – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919248/

[28] Naturally occurring anti-cancer agents targeting EZH2 – https://www.ncbi.nlm.nih.gov/pubmed/28323035

[29] Biological evaluation of tanshindiols as EZH2 histone methyltransferase inhibitors – https://www.ncbi.nlm.nih.gov/pubmed/24767850

[30] Melatonin inhibits tumorigenicity of glioblastoma stem-like cells via the AKT-EZH2-STAT3 signaling axis – https://www.ncbi.nlm.nih.gov/pubmed/27121240

DISCLAIMER: The purpose of this article is to provide information. It should not be interpreted as medical advice, and is not intended to diagnose, treat or cure any medical condition, or to be a substitute for advice from your health care professional.  If you have breast cancer, it is important that you work closely with a health care professional to properly treat your condition and monitor your progress.

GET MY BEST TIPS on getting through breast cancer and preventing recurrences by signing up for my free e-newsletters and e-books on the right. You can also “like” me on Facebook (Marnie Clark, Breast Health Coach) to get my inspirational snippets, news and updates. I promise to do my utmost to keep you informed and empowered on your healing journey… and beyond.