Protecting Bones From Breast Cancer Metastasis

Yesterday I posted on my Facebook business page (Marnie Clark, Breast Health Coach) a very interesting article about a study that had researchers investigating how it is possible that breast cancer cells from a primary tumor migrate to the bones. Researchers were looking into what was happening in the bones that allowed cancer cells to remain there dormant, only to reawaken decades later. They wanted to understand how breast cancer cells were able to flourish through metastasis to the bone – this has long been a goal of the breast cancer research community, according to one of the lead research team members, Dr Karen Bussard.

That very thing has long worried me as well, particularly because I had breast cancer 15 years ago – and in my role as a breast health coach I do run into people that this has happened to – they were cancer-free for 20 years, and then suddenly they incur a bone fracture and it is found that their breast cancer is in their bones and they are deemed to be at Stage 4. So this research really interested me, and in view of the amount of interest it engendered on my Facebook page, it’s obvious that many others want to know more as well. Here is a synopsis of the research, and under that I share a list of the nutrients that help to protect bones from metastasis by breast cancer cells.

The Research

The study [1] was done in 2018 at Thomas Jefferson University at the Sidney Kimmel Cancer Center in Philadelphia, PA. I would invite you to take the time to read this study as it is fascinating. Researchers investigated how bone cells change once they interact with breast cancer cells. They found that osteoblasts (a bone cell that is responsible for the deposition of new bone matrix) from mice and humans change their function after interacting with breast cancer cells that had migrated to the bones. Osteoblasts apparently have multiple roles in the progression of cancer and appear to interact differently with cancer cells depending on the stage of the disease.

First, I’ll share with you the introduction to this research because it’s important for us to understand how bone cells work. “In a cancer-free environment in the adult, the skeleton continuously undergoes remodeling. Bone-resorbing osteoclasts excavate erosion cavities, and bone-depositing osteoblasts synthesize osteoid matrix that forms new bone, with no net bone gain or loss. When metastatic breast cancer cells invade the bone, this balance is disrupted. Patients with bone metastatic breast cancer frequently suffer from osteolytic bone lesions that elicit severe bone pain and fractures.”

Earlier studies showed that in advanced stage metastatic breast cancer (let’s call this ASMBC) patients where bones were invaded, osteoblasts stopped working – they didn’t produce the matrix that strengthens and stabilizes bone, which is what leads to the loss of bone density that is seen in these patients. Apparently in ASMBC, cancer cells are able to co-opt osteoblasts to help the cancer cells thrive.

The researchers in this study found that in earlier stages of breast cancer when cancer cells first enter bones, instead of producing new bone matrix, the osteoblasts can divert their energy toward producing factors to stop the growth of the invading cancer cells. These osteoblasts, now termed “tumor-educated osteoblasts”, release factors that change the behavior of the cancer cells – these factors check the wild growth of the cancer cells and restore the function of the P21 gene which stops the proliferation of metastatic breast cancer cells. Fascinating, right?

The research team also found that these tumor-educated osteoblasts were able to slow the growth of the cancer. However, the osteoblasts that did not meet up and interact with metastatic breast cancer cells did not have the ability to slow cancer cell growth.

Dr Bussard stated “The next step is to fully characterize the molecules that osteoblasts use to reign in cancer growth, and see whether it’s possible to turn that understanding toward treatments that can put cancer cells to sleep forever.” [2]

In the meantime, while we’re waiting for that research, there are things we can do as breast cancer survivors to promote good bone health.

Phytochemicals that Promote Strong Osteoblasts

Phytochemicals are plant-based chemicals – all natural – and these are the ones I have found (so far – there may well be more) that promote strong osteoblasts.

Cannibidiol – available by supplementation [26]

Cinnamic acid – found in adzuki beans, amaranth, apples, apricots, arugula (rocket), avocados, bell peppers, bitter melon, black beans, blackberries, bok choy, brown rice, cabbage, carrots, cauliflower, cherries, celery, chickpeas, chilies and hot peppers, cranberries, dragon fruit, durian, figs, flaxseed, goji, graviola, kale, kiwi, kohlrabi, lemons, macadamia nuts, mandarins, mangosteen, maqui, nectarines, oranges, peaches, pears, peas, pineapple, pomegranates, quinoa, rice bran, rutabaga, sorghum bran, soybeans, spelt, strawberries, sunflower seeds, tomatoes, turnips, walnuts, wasabi, wheat bran [3]

Epicatechin gallate – found in apples, apricots, berries, cherries, chocolate, cocoa beans, grapes (black and red), onions, pears, tea (green and black) [4]

Genistein – found in chickpeas, dates, kidney beans, peanuts, peas, pomegranates, quinoa, soybeans [5]

Kaempferol – found in almonds, amla, Anasazi beans, apples, arugula (rocket), asparagus, barley, beets, bell peppers, black beans, black-eyed peas, black raspberries, black rice, blackberries, blackcurrants, blueberries, bok choy, broccoli, Brussel sprouts, buckwheat bran, cantaloupe, cauliflower, celery, cherries, chickpeas, chia seeds, collard greens, cranberries, dates, dragon fruit, elderberries, flaxseed, ginkgo biloba, goji/wolfberry, grapefruit, grapes, graviola, green beans, guava, horseradish, kale, kidney beans, kiwi, kohlrabi, lemons, lentils, lima beans, limes, lychee, mangoes, maqui, mulberries, nectarines, noni, passionfruit, peaches, pears, peas, persimmons, pomegranates, pumpkin seeds, quinoa, radishes, raspberries, red beans, rice bran, rutabaga, sesame seeds, spelt, strawberries, sunflower seeds, tomatoes, turnips, watercress, watermelon [6]

Monotropein – found in bilberries, mulberries [7]

Naringenin, naringin – grapefruit, lemon, lime, pomegranate [8], [9]

Quercetin – found in adzuki beans, almonds, amla, Anasazi beans, apples with peels, apricots, arugula (rocket), asparagus, avocados, bananas, barley, beets, bell peppers, bilberries, black beans, black-eyed peas, black raspberries, black rice, black tea, blackberries, blackcurrants, blueberries, bok choy, Brazil nuts, broccoli, brown rice, Brussel sprouts, cantaloupe, capers, cauliflower, celery, cherries, chickpeas, chia seeds, chilies and hot peppers, cocoa powder (unsweetened), collard greens, cranberries, daikon, dates, dill, dragon fruit, durian, eggplant, elderberries, figs, gingko biloba, goji, grapefruit, grapes, graviola, green beans, green pepper, green tea, guava, honey, honeydew melon, horseradish, kale, kiwi, kohlrabi, lemons, lentils, lettuce (esp Romaine), lima beans, limes, lychee, mangoes, maqui, mulberries, nectarines, noni, onions, parsley, passionfruit, peaches, pears with peels, peas, peppers, persimmons, pigeon pea leaves & seeds, pineapple, plums, pomegranates, pumpkin seeds, quinoa, radishes, raspberries, red onions, rutabaga, sage, sesame seeds, shallots, spelt, spinach, strawberries, sunflower seeds, tea (black and green), tomatoes, turnips, watercress, yellow snap beans [10]

Taxifolin – found in avocados, Brazil nuts, lemons, limes, spelt [11]

Vitamin D3 – found in raw milk, salmon, sunshine, tuna, and via supplementation [12]

Phytochemicals that Inhibit Bone Cancer Metastases

These are the phytochemicals that studies have shown inhibit bone cancer metastases. There will be significantly more than these, and as I locate them, I will add them here.

Betulinic acid – found in chaga mushrooms, persimmons, pomegranates [13]

Esculin – found in guava, plums [28]

Isothiocyanates – found in cruciferous vegetables, ie arugula (rocket), bok choy, broccoli, broccoli sprous, Brussel sprouts, cabbage, cauliflower, collard greens, daikon, horseradish, kale, kohlrabi, papaya, radishes, rutabaga, turnips, wasabi, watercress [14]

Vitamin K2 – found in apples, arugula (rocket), asparagus, avocados, bananas, barley, bell peppers, black-eyed peas, black raspberries, blackberries, blackcurrants, blueberries, bok choy, broccoli, Brussel sprouts, cabbage, cannellini beans, cantaloupe, carrots, cashews, cauliflower, celery, cherries, chilies and hot peppers, collard greens, cranberries, cucumbers, dandelion greens, figs, grapes, green beans, guava, honeydew melon, horseradish, kale, kelp, kidney beans, kiwi, kohlrabi, lima beans, mangoes, mulberries, mustard greens, nectarines, papayas, peaches, pears, peas, persimmons, pine nuts, pineapple, plums, pomegranates, radishes, raspberries, rutabaga, spelt, spinach, spring onions, strawberries, Swiss chard, tomatoes, turnips & turnip greens, watercress, watermelon, and available by supplementation [15]

Phytochemicals that Promote P21 Gene Activity

Since it looks as though the P21 gene is also involved in bone health and a therapeutic target, promoting the activity of that gene would certainly make sense. Here are the phytochemicals that do this:

Coumestrol – found in dates, peas, pomegranates, soybeans [27]

Damnacanthal and nordamnacanthal – found in noni fruit and juice [16]

Diosmin – found in mandarins and oranges [17]

Genistein – see entry above for list of foods [18]

Indole-3-carbinol – found in cruciferous veggies ie arugula (rocket), bok choy, broccoli, broccoli sprouts, Brussel sprouts, cabbage, cauliflower, collard greens, daikon, horseradish, kale, kohlrabi, radishes, rutabaga, turnips, watercress [19]

Momilactone B – found in brown rice [20]

Nobiletin – found in grapefruit, lemons, limes, mandarins, oranges, tangerines [21]

Don’t Forget the Selenium

Selenium – found in amaranth, asparagus, barley, black-eyed peas, blackberries, Brazil nuts, brewer’s yeast, broccoli, brown rice, buckwheat bran, chickpeas, chicken, dates, einkorn, garlic, goji/wolfberry, grapefruit, guava, honeydew melon, kelp, lentils, lima beans, liver, macadamia nuts, mangoes, molasses, mulberries, noni, oats, onions, peanuts, pears, pecans, pistachio nuts, pumpkin seeds, quinoa, radishes, red beans, salmon, seafood, sesame seeds, spelt, spinach, strawberries, sunflower seeds, turnips, walnuts, watermelon, wheat bran, wheat germ. Selenium may also be helpful for those with breast cancer that has metastasized to the bones. A 2009 study [22] found that selenium played a role in suppressing the complicated inflammatory response in this type of cancer. Selenium has many other roles to play in breast cancer prevention, it is one of my most-often prescribed supplements to my clients.
The main role of selenium is to inhibit the oxidation of fats as one of the components in the enzyme glutathione peroxidase, one of the most powerful antioxidants in the body. Selenium alters many different genes to make the body less susceptible to cancer and most people are deficient in this important mineral. Selenium also protects the immune system, especially when combined with vitamin E. Most importantly, selenium protects breast cells from oxidative DNA damage, and inhibits the initiation phase of carcinogenesis by stimulating DNA repair, regulating apoptosis and preventing angiogenesis. Selenium also stimulates the production of T cells in the immune system. [23] Another good thing that selenium does for us – in the form of methyl-seleninic acid, is that it is a natural aromatase inhibitor. [24] You can see why I recommend it so frequently!

The Importance of Exercise

Remember that exercise is also crucially important for healthy bones. Muscles move bones and in response to that pulling and tugging, osteoblasts and osteoclasts kick into gear and the process of bone building and resorption begins. Bone mineral content and bone mineral density are 20% higher in athletes than in the general population. You don’t have to be an athlete though – just get out there and move. Whether you choose weight-lifting, dancing, gardening, running, tai chi, hiking, walking, yoga (my personal favorite), Pilates, bicycling – whatever it is you like to do, get out there and move on a daily basis. It’s one of the best things you can do for your bones.

So between drenching your body in all of the foods that contain those protective phytochemicals and undertaking daily exercise, you give yourself a much better chance of avoiding metastatic breast cancer.

References:

[1] Osteoblasts are “educated” by crosstalk with metastatic breast cancer cells in the bone tumor microenvironment – https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-019-1117-0

[2] Bone cells suppress cancer metastases – https://www.sciencedaily.com/releases/2019/05/190513104507.htm

[3] The botanical molecule p-hydroxycinnamic acid as a new osteogenic agent: insight into the treatment of cancer bone metastases – https://www.ncbi.nlm.nih.gov/pubmed/27573001

4-Epicatechin gallate (ECG) stimulates osteoblast differentiation via Runt-related transcription factor 2 (RUNX2) and transcriptional coactivator with PDZ-binding motif (TAZ)-mediated transcriptional activation – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975037/

[5] Genistein stimulates the osteoblastic differentiation via NO/cGMP in bone marrow culture – https://www.ncbi.nlm.nih.gov/pubmed/15526288

[6] Stimulatory effect of naturally occurring flavonols quercetin and kaempferol on alkaline phosphatase activity in MG-63 human osteoblasts through ERK and estrogen receptor pathway – https://www.sciencedirect.com/science/article/abs/pii/S0006295203009006

[7] Monotropein isolated from the roots of Morinda officinalis increases osteoblastic bone formation and prevents bone loss in ovariectomized mice – https://www.ncbi.nlm.nih.gov/pubmed/26996879

[8] Naringin-induced bone morphogenetic protein-2 expression via PI3K, Akt, c-Fos/c-Jun and AP-1 pathway in osteoblasts – https://www.sciencedirect.com/science/article/pii/S0014299908004585

[9] Naringin promotes osteoblast differentiation and effectively reverses ovariectomy-associated osteoporosis – https://link.springer.com/article/10.1007/s00776-013-0362-9

[10] Stimulatory effect of naturally occurring flavonols quercetin and kaempferol on alkaline phosphatase activity in MG-63 human osteoblasts through ERK and estrogen receptor pathway – https://www.sciencedirect.com/science/article/abs/pii/S0006295203009006

[11] Taxifolin enhances osteogenic differentiation of human bone marrow mesenchymal stem cells partially via NF-kB pathway – https://www.ncbi.nlm.nih.gov/pubmed/28579433

[12] 24R,25-dihydroxyvitamin D3 promotes the osteoblastic differentiation of human mesenchymal stem cells – https://www.ncbi.nlm.nih.gov/pubmed/24597546

[13] Betulinic acid, a bioactive pentacyclic triterpenoid, inhibits skeletal-related events induced by breast cancer bone metastases and treatment – https://www.ncbi.nlm.nih.gov/pubmed/24463094

[14] Benzyl isothiocyanate prevents breast cancer-induced bone erosion in vivo – http://cancerres.aacrjournals.org/content/77/13_Supplement/5258

[15] Effect of vitamin K in bone metabolism and vascular calcification: A review of mechanisms of action and evidences – https://www.ncbi.nlm.nih.gov/pubmed/27437760

[16] Damnacanthal is a potent inducer of apoptosis with anticancer activity by stimulating p53 and p21 genes in MCF-7 breast cancer cells – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997671/

[17] Diosmin-induced senescence, apoptosis and autophagy in breast cancer cells of different p53 status and ERK activity – https://www.ncbi.nlm.nih.gov/pubmed/27890807

[18] AKT and p21 WAF1/CIP1 as potential genistein targets in BRCA1-mutant human breast cancer cell lines – https://www.ncbi.nlm.nih.gov/pubmed/20651350

[19] The indole-3-carbinol cyclic tetrameric derivative CTet inhibits cell proliferation via overexpression of p21/CDKN1A in both estrogen receptor-positive and triple-negative breast cancer cell lines. — https://www.ncbi.nlm.nih.gov/pubmed/21435243

[20] Momilactone B induces apoptosis and G1 arrest of the cell cycle in human monocytic leukemia U937 cells through downregulation of pRB phosphorylation and induction of the cyclin-dependent kinase inhibitor p21Waf1/Cip1 – https://www.ncbi.nlm.nih.gov/pubmed/24503697

[21] Antiproliferative and apoptosis-inducing activity of nobiletin against three subtypes of human breast cancer cell lines – https://www.ncbi.nlm.nih.gov/pubmed/24692711

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

[23] Selenium and anticarcinogenesis: underlying mechanisms – https://www.ncbi.nlm.nih.gov/pubmed/18827575/

[24] Methylseleninic acid is a novel suppressor of aromatase expression – https://www.ncbi.nlm.nih.gov/pubmed/22128327

[25] Diet and Exercise: a Match Made in Bone – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705732/

[26] Cannibinoids and bone regeneration —
https://www.ncbi.nlm.nih.gov/pubmed/30702341

[27] Cytotoxic activity of soy phytoestrogen coumestrol against human breast cancer MCF-7 cells: Insights into the molecular mechanism – https://www.ncbi.nlm.nih.gov/pubmed/27913286

[28] Aesculin modulates bone metabolism by suppressing receptor activator of NF-kB ligand (RANKL)-induced osteoclastogenesis and transduction signals – https://www.ncbi.nlm.nih.gov/pubmed/28465233

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