Epigenetic Factors to Reduce Breast Cancer Risk – Part 10
This is part 10 of an 11-part series of articles, covering the epigenetic factors that reduce the growth of breast cancer cells and breast cancer risk. My intention with these articles is to empower you with information to help you heal from breast cancer, reduce your risk of recurrence, and/or to reduce your risk of getting breast cancer.
For more information on my personal reasons for putting this information together, see Part 1 of the series.
In this article, I am sharing the nutrients that block angiogenesis (angio = related to blood vessels, and genesis = the creation of something new). Once a tumor begins developing and is in its rapid growth stage, it needs a fresh blood supply to feed itself and to migrate into other tissues (metastasize). The cells of a developing tumor have the ability to induce the growth of new blood vessels, termed angiogenesis, and they do this by multiple epigenetic mechanisms. So knowing what nutrients are capable of reversing the angiogenesis process is tremendously important because then you can deprive growing tumors of that new blood supply.
PART 10 – NUTRIENTS THAT BLOCK ANGIOGENESIS
Anthocyanins – found in acai, Anasazi beans, apples, bananas, black beans, bilberries, black raspberries, black rice, blackcurrants, blueberries, chickpeas, cranberries, elderberries, grapes, guava, kidney beans, mangoes, mangosteen, maqui, pomegranates, purple beans, purple carrots, purple sweet potatoes, sorghum bran, strawberries, walnuts [1]
Apigenin – found in celery, chamomile tea, chickpeas, dates, elderberries, grapefruit, guava, lemons, limes, onions, oranges, parsley, peas, rice bran, sorghum bran [2]
Beta-sitosterol – found in acai, almonds, amaranth, bananas, barley, black rice, blackberries, Brazil nuts, dates, dragon fruit, durian, flaxseed, goji, hemp seed, kiwi, macadamia nuts, oats, peas, pecans, pistachio nuts, pumpkin seeds, quinoa (more on quinoa here), raspberries, rice bran, sesame seeds, soybeans, sunflower seeds, walnuts, wheat, wheat bran [3]
Betulinic acid – found in chaga mushrooms, pomegranate, white birch bark [4]
Chebulagic acid – found in amla, myrobalan (Terminalia chebula) [5]
Coenzyme Q10 (CoQ10), a supplement [6]
Conjugated linoleic acid (CLA) – found in organic grass fed beef, butter from grass-fed cows raised organically, full fat (preferably raw, organic) dairy products like cream, milk, yogurt or cheese [7]
Curcumin – found in turmeric; also available in supplements [8]
Durianol – found in durian [9]
Enterolactone – found in flaxseed, oats [10]
Esculin – found in guava [11]
Fisetin – found in apples, cucumbers, grapes, kiwi, onions, persimmon, strawberries [12]
Formononetin – found in astragalus, cashews, dates, red clover [13]
Genistein – found in chickpeas, dates, kidney beans, peas, quinoa, soybeans [14], [10]
Grape seed extract – a supplement [15]
Green tea [16], [17]
Indole-3-Carbinol (I3C) – found in cruciferous vegies such as cabbage, radishes, cauliflower, broccoli, Brussels sprouts, and daikon; also available in supplement form [18]
Jasmonic acid – found in apples, chickpeas, jasmine essential oil [19]
Juglone – from walnuts [20]
Luteolin – found in cantaloupe, celery, dates, elderberries, graviola, lemongrass, lemons, lentils, limes, maqui, oregano, parsley, peas, peppermint, pomegranate, rice bran, rosemary, sorghum bran [21]
Lycopene – found in apricots, bitter melon, dragon fruit, goji, grapefruit, guava, mangoes, pistachio nuts, tomatoes, red beans [22], [23]
Melatonin – found in bananas, barley, black rice, cherries (esp sour), ginger, grapes, oats, walnuts, also available as a supplement [24]
Nobiletin – found in grapefruit, lemons, limes, mandarins, oranges, tangerines [25]
Omega-3 fatty acids – found in many fish, but best plant source is from flaxseed oil or hempseed oil; also available as supplements [26]
Orientin and isoorientin – found in acai, graviola [27]
Piceatannol – found in blackberries, blueberries, cranberries, grapes [28]
Pomegranate [29], [30]
Quercetin – found in adzuki beans, amla, Anasazi beans, apples with peels, apricots, asparagus, bananas, barley, bilberries, black beans, black raspberries, black rice, black tea, blackberries, blackcurrants, blueberries, broccoli, cantaloupe, capers, cauliflower, celery, cherries, chickpeas, chia seeds, cocoa powder (unsweetened), cranberries, dates, dill, dragon fruit, durian, eggplant, elderberries, figs, gingko biloba, goji, grapefruit, grapes, graviola, green beans, green pepper, green tea, guava, honey, kale, kiwi, lemons, lentils, lettuce (esp Romaine), limes, lychee, mangoes, maqui, mulberries, onions, parsley, peas, pears with peels, peppers, quinoa, raspberries, red onions, sage, shallots, spinach, strawberries, tea (black and green), tomatoes, yellow snap beans [31]
Selenium – found in amaranth, barley, Brazil nuts, brewer’s yeast, broccoli, brown rice, buckwheat bran, chickpeas, chicken, dates, garlic, goji, guava, kelp, lentils, liver, macadamia nuts, mangoes, molasses, oats, onions, pecans, pistachio nuts, pumpkin seeds, quinoa, red beans, salmon, seafood, spelt, sunflower seeds, walnuts, wheat, wheat bran, wheat germ [32]
Silibinin – found in St Mary’s Thistle a/k/a milk thistle [33]
Sulforaphane – found in cruciferous vegetables, broccoli sprouts [34], [35]
Syringic acid – found in acai, barley, bitter melon, dates, figs, flaxseed, kiwi, molasses, mulberries, rice bran, sorghum bran, swiss chard, walnuts, wheat [36], [37]
Tricin – found in rice bran, brown rice [38]
Vitamin D3 – found in raw milk, salmon, sunshine, tuna; also available in supplement form [39], [40]
2′-hydroxyflavonone – found in grapefruit, lemons, limes, mandarins, oranges, tangerines [41]
This is not an exhaustive list of nutrients, there are likely others that block the angiogenesis process in breast cancer cells. As I find the research and nutrients, I will add them here. With reference to therapeutic dosages, because much of the research is preliminary and has not been involved in a clinical trial, it is not known what exact amount is required for many of these nutrients to block angiogenesis. But because everything listed is nutritional with no known side effects, (unless you are allergic), my advice would be to include as many of these nutrients in your daily/weekly diet as possible.
IMPORTANT NOTE: Please do not attempt to treat breast cancer using only a few nutrients or supplements. Cancer is a complex disease and requires a multi-disciplinary approach to be effective. Please work with an oncologist and/or integrative oncologist and/or oncology naturopath and/or functional medicine doctor for the absolute best results.
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
Part 3 nutrients that stop rapid proliferation of cells
Part 4 nutrients that ease cancer promoting inflammation
Part 5 nutrients that change malignant cells back into healthy cells
Part 6 nutrients that alter or restore receptors on breast cancer cells
Part 7 nutrients that inhibit excess estrogen production
Part 8 nutrients that trigger apoptosis in breast cancer cells
Part 9 nutrients that block abnormal growth factors
References:
[1] Anthocyanins and their role in cancer prevention – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2582525/
[2] Apigenin blocks induction of vascular endothelial growth factor mRNA and protein in progestin-treated human breast cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/20551847
[3] Beta-Sitosterol: A Promising but Orphan Nutraceutical to Fight Against Cancer – https://www.ncbi.nlm.nih.gov/pubmed/26473555
[4] Multiple molecular targets in breast cancer therapy by betulinic acid – https://www.ncbi.nlm.nih.gov/pubmed/27810789
[5] Anti-angiogenic effect of chebulagic acid involves inhibition of the VEGFR2- and GSK-3ß-dependent signaling pathways – https://www.ncbi.nlm.nih.gov/pubmed/28467858
[6] Coenzyme Q10 decreases basic fibroblast growth factor (bFGF)-induced angiogenesis by blocking ERK activation – https://www.ncbi.nlm.nih.gov/pubmed/22715588
[7] Prevention of mammary cancer with conjugated linoleic acid: role of the stroma and the epithelium – https://www.ncbi.nlm.nih.gov/pubmed/14587866
[8] The impact of curcumin on breast cancer – https://www.ncbi.nlm.nih.gov/pubmed/22772921
[9] Plant phenolics in the prevention and treatment of cancer – https://www.ncbi.nlm.nih.gov/pubmed/21520702
[10] 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
[11] Esculin and its oligomer fractions inhibit adhesion and migration of U87 glioblastoma cells and in vitro angiogenesis – https://www.ncbi.nlm.nih.gov/pubmed/26459313
[12] The flavonoid fisetin as an anticancer agent targeting the growth signaling pathways – https://www.sciencedirect.com/science/article/pii/S0014299916304319?via%3Dihub
[13] Formononetin, a novel FGFR2 inhibitor, potently inhibits angiogenesis and tumor growth in preclinical models – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792576/
[14] Genistein exerts multiple suppressive effects on human breast carcinoma cells – https://www.ncbi.nlm.nih.gov/pubmed/9809990
[15] Grape seed extract (GSE) inhibits angiogenesis via suppressing VEGFR signaling pathway – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2802543/
[16] Inhibition of mammary tumorigenesis in the C3(1)/SV40 mouse model by green tea – https://www.ncbi.nlm.nih.gov/pubmed/17484049
[17] Green tea catechins inhibit angiogenesis through suppression of STAT3 activation – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664280/
[18] Molecular targets and anticancer potential of indole-3-carbinol and its derivatives – https://www.ncbi.nlm.nih.gov/pubmed/16082211
[19] Methyl jasmonate abolishes the migration, invasion and angiogenesis of gastric cancer cells through down-regulation of matrix metalloproteinase 14 – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576238/
[20] 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
[21] Inhibitory effect of luteolin on the angiogenesis of chick chorioallantoic membrane and invasion of breast cancer cells via downregulation of AEG-1 and MMP-2 – https://www.ncbi.nlm.nih.gov/pubmed/24129732
[22] Chemopreventive effect of lycopene alone or with melatonin against the genesis of oxidative stress and mammary tumors induced by 7,12 dimethyl(a)benzanthracene in sprague dawely female rats – https://www.ncbi.nlm.nih.gov/pubmed/18682897
[23] Lycopene inhibits angiogenesis both in vitro and in vivo by inhibiting MMP-2/uPA system through VEGFR2-mediated PI3K-Akt and ERK/p38 signaling pathways – https://www.ncbi.nlm.nih.gov/pubmed/22707264
[24] Melatonin regulates the tumor suppressor miR-148a-3p involved in angiogenesis and metastasis of breast cancer – http://cancerres.aacrjournals.org/content/77/13_Supplement/1477
[25] Nobiletin Inhibits Angiogenesis by Regulating Src/FAK/STAT3-Mediated Signaling through PXN in ER+ Breast Cancer Cells – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454848/
[26] Regulation of tumor angiogenesis by dietary fatty acids and eicosanoids – https://www.ncbi.nlm.nih.gov/pubmed/11142082
[27] Isoorientin induces apoptosis, decreases invasiveness, and downregulates VEGF secretion by activating AMPK signaling in pancreatic cancer cells – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161403/
[28] Inhibition of tumor progression by oral piceatannol in mouse 4T1 mammary cancer is associated with decreased angiogenesis and macrophage infiltration – https://www.ncbi.nlm.nih.gov/pubmed/26297476
[29] Preliminary studies on the anti-angiogenic potential of pomegranate fractions in vitro and in vivo – https://www.ncbi.nlm.nih.gov/pubmed/14739618
[30] Punicalagin, a polyphenol from pomegranate fruit, induces growth inhibition and apoptosis in human PC-3 and LNCaP cells – https://www.ncbi.nlm.nih.gov/pubmed/28709945
[31] Quercetin Suppresses Cyclooxygenase-2 Expression and Angiogenesis through Inactivation of P300 Signaling – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152552/
[32] Selenium and anticarcinogenesis: underlying mechanisms – https://www.ncbi.nlm.nih.gov/pubmed/18827575/
[33] Silibinin prevents TPA-induced MMP-9 expression and VEGF secretion by inactivation of the Raf/MEK/ERK pathway in MCF-7 human breast cancer cells –
https://www.ncbi.nlm.nih.gov/pubmed/19181503
[34] Sulforaphane–a possible agent in prevention and therapy of cancer – https://www.ncbi.nlm.nih.gov/pubmed/21160094/
[35] Epigenetic diet: impact on the epigenome and cancer – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197720/
[36] Syringic acid from Tamarix aucheriana possesses antimitogenic and chemo-sensitizing activities in human colorectal cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/23745612
[37] Mechanistic Study of the In Vitro and In Vivo Inhibitory Effects of Protocatechuic Acid and Syringic Acid on VEGF-Induced Angiogenesis – https://www.ncbi.nlm.nih.gov/pubmed/29886729
[38] Tricin, 4′,5,7-trihydroxy-3′,5′-dimethoxyflavone, exhibits potent antiangiogenic activity in vitro – https://www.ncbi.nlm.nih.gov/pubmed/27498749
[39] The Potential Therapeutic Benefits of Vitamin D in the Treatment of Estrogen Receptor Positive Breast Cancer – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3429709/
[40] Vitamin D3 decreases glycolysis and invasiveness, and increases cellular stiffness in breast cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/29216499
[41] 2′-Hydroxyflavanone: A novel strategy for targeting breast cancer – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650397/
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