Epigenetic Factors to Reduce Breast Cancer Risk – Part 11

Epigenetic Factors to Reduce Breast Cancer Risk – Part 11

This is the final segment in my 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 has been to show you exactly what nutrients will help you heal from breast cancer, reduce your risk of recurrence, and/or reduce your risk of ever getting breast cancer.

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

In this segment, I am sharing the nutrients that prevent metastasis, which is the spread of cancer from one part of the body to another. A growing tumor can become invasive and it does this in a few different ways. Malignant cells can break away from the original tumor, and enter the bloodstream or lymphatic system, which can carry them to another part of the body. A tumor may also increase production of enzymes called matrix metalloproteinases, or MMPs. These enzymes degrade proteins in surrounding tissues, thus enabling a tumor to spread. Recent research suggests that MMPs are involved in breast cancer initiation, invasion and metastasis. Two MMPs in particular (MMP-2 and MMP-11) have been found to correlate with a poor prognosis in patients with breast cancer. [1] So nutrients that can impair a tumor’s production of MMPs, and reduce the invasiveness and metastatic potential is thought to be a good strategy for fighting against breast cancer.

Here they are – the best nutrients for preventing or impairing the metastasis of breast cancer cells.

PART 11 – NUTRIENTS THAT PREVENT OR IMPAIR METASTASIS

Anthraquinones – found in aloe vera, graviola, noni, rhubarb [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, noni, oats, peas, pecans, pistachio nuts, pumpkin seeds, quinoa, raspberries, rice bran, sesame seeds, soybeans, sunflower seeds, walnuts, watermelon, wheat, wheat bran [3]

Biochanin A – found in alfalfa sprouts, astragalus, cashews, chickpeas, kidney beans, pinto beans, red clover [4]

Chebulinic acid – found in amla, myrobalan [5]

Chlorogenic acid – found in almonds, apples, bitter melon, black beans, black raspberries, blackberries, blackcurrants, blueberries, cherries, chia seeds, chickpeas, coffee beans, durian, figs, goji, graviola, guava, kiwi, lentils, lychee, mulberries, raspberries, rice bran, sunflower seeds, tomatoes [6]

Coenzyme Q10 (CoQ10) – supplement [7]

Conjugated linoleic acid (CLA) – from organic grass fed beef, butter from grass-fed cows raised organically, full fat (preferably raw) dairy products like cream, milk, yogurt or cheese [8]

Curcumin – from turmeric [9], [10]

Delphinidin – found in acai, amla, bananas, bilberries, black raspberries, blackcurrants, black beans, blueberries, cherries, cranberries, kidney beans, maqui, raspberries [11], [12]

Epigallocatechin-3-gallate (EGCG) – found in amla, carob flour, cranberries (raw), hazlenuts, peas, pecans, tea (black, green, oolong) [13], [14], [15]

Fisetin – found in apples, cucumbers, grapes, kiwi, onions, persimmon, strawberries [16], [17]

Gallic acid – from adzuki beans, amaranth, amla, apples, apricots, bitter melon, black raspberries, blackberries, blueberries, cantaloupe, cherries, chickpeas, dates, dragon fruit, durian, eggplant, evening primrose oil, figs, flaxseed, goji/wolfberry, grapes, graviola, hazelnuts, kiwi, lentils, lychee, mangoes, mangosteen, maqui, mulberries, peas, pecans, pumpkin seeds, quinoa, raspberries, red beans, soybeans, strawberries, walnuts, watermelon [18]

Gamma-tocotrienol – found in barley, blueberries, brown rice, coconut oil, cod liver oil, corn oil, cranberries, flaxseed oil, hazlenuts, kiwi, oats, olive oil, peanut oil, plums, rice bran oil, rye, sunflower oil, wheat germ [19]

Genistein – from chickpeas, dates, kidney beans, peas, quinoa, soybeans [20], [21]

Glycyrrhetinic acid – from licorice (the herbal, not the candy) [22]

Isothiocyanates – found in cruciferous vegetables, papaya [23]

Kahweol – found in unfiltered coffee [24]

Lupeol – found in cabbage, carrots, cucumber, figs, grapes (red), guava, mango, mulberries, olives, papaya, peas, peppers (capsicum), soybeans, strawberry, tomato [25]

Luteolin – found in cantaloupe, celery, dates, elderberries, graviola, lemongrass, lemons, lentils, limes, maqui, noni, oregano, parsley, peas, peppermint, pomegranate, rice bran, rosemary, sorghum bran, watermelon [26]

Lycopene – from apricots, bitter melon, dragon fruit, goji, grapefruit, guava, mangoes, noni, papaya, pistachio nuts, tomatoes, red beans, watermelon [27]

Mangostin – from mangosteen [28]

Melatonin – from bananas, barley, black rice, cherries (esp sour), ginger, grapes, oats, walnuts [29]

Modified Citrus Pectin – supplement [30]

Myricetin – from adzuki beans, barley, bitter melon, black beans, blackberries, blackcurrants, blueberries, chia seeds, chickpeas, cranberries, fennel, grapes, guava, maqui, parsley [31]

N-acetylcysteine (NAC) – supplement [32]

Naringenin – from almonds, black rice, elderberries, grapefruit, kiwi, lemons, limes, mandarins, oranges, peas, rice bran, sorghum bran, tangerines [33]

Nornuciferine – from graviola [34]

Psoralen – found in carrots, celeriac, celery, cilantro/coriander, cumin seeds, dill, fennel seeds, figs, grapefruit, lemons, limes, mustard seeds, parsley, parsnips [35]

Silibinin – found in St Mary’s thistle a/k/a milk thistle [36], [37], [38], [39]

Sulforaphane – found in cruciferous vegetables [40]

Tricin – found in rice bran, brown rice [41]

Ursolic Acid – found in cherries, cranberries, elderberries, grapes, kiwi, maqui, noni [42]

Vanillic acid – found in acai, barley, bilberries, bitter melon, black raspberries, blackberries, brown rice, buckwheat bran, cantaloupe, chickpeas, clove, dates, flaxseed, kiwi, mangosteen, maqui, mulberries, peas, pecans, quinoa, raspberries, rice bran, shiitake mushrooms, strawberries, vanilla beans, wheat, wheat bran [43], [44]

Vitamin D3 – found in raw milk, salmon, sunshine, tuna, supplements [45]

Zeaxanthin – found in bananas, barley, black raspberries, blackcurrants, blueberries, cantaloupe, carrots, cashews, cranberries, durian, figs, goji, grapefruit, grapes, green beans, honeydew melon, kiwi, lemons, mandarins, mangoes, mulberries, oranges, papaya, peas, pecans, pistachio nuts, quinoa, raspberries, spelt, strawberries, walnuts, watermelon, wheat, wheat bran [46]

2′-hydroxyflavonone – found in grapefruit, lemons, limes, mandarins, oranges, tangerines [47]

Aspirin – though not a nutrient, we have interesting research on its anti-metastasis potential [48]

This is not an exhaustive list of nutrients that prevent or impair metastasis, there are likely others that have this action. As I find the research, I will add it 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 do their work. But because everything listed is nutritional, with no known side effects (outside of the last one, aspirin) my advice is to include as many of them in your daily/weekly diet as you can.

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

Part 10 nutrients that block angiogenesis

References:

[1] Metalloproteinases: role in breast carcinogenesis, invasion and metastasis – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC138784/

[2] 3-Bromo-1-hydroxy-9,10-anthraquinone (BHAQ) inhibits growth and migration of the human breast cancer cell lines MCF-7 and MDA-MB231 – https://www.ncbi.nlm.nih.gov/pubmed/23985955

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

[4] The selective estrogen receptor-beta agonist biochanin A shows vasculoprotective effects without uterotrophic activity – https://www.ncbi.nlm.nih.gov/pubmed/16735947

[5] Chebulinic acid inhibits smooth muscle cell migration by suppressing PDGF-Rß phosphorylation and inhibiting matrix metalloproteinase-2 expression – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603554/

[6] A phenolic compound, 5-caffeoylquinic acid (chlorogenic acid), is a new type and strong matrix metalloproteinase-9 inhibitor: isolation and identification from methanol extract of Euonymus alatus – https://www.ncbi.nlm.nih.gov/pubmed/16005473

[7] 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/

[8] CLA reduces breast cancer cell growth and invasion through ERalpha and PI3K/Akt pathways – https://www.ncbi.nlm.nih.gov/pubmed/19800873

[9] Curcumin Suppresses the Paclitaxel-Induced Nuclear Factor-KB Pathway in Breast Cancer Cells and Inhibits Lung Metastasis of Human Breast Cancer in Nude Mice – http://www.jivasupplements.org/assets/applets/Curcumin_Suppresses_the_Paclitaxel-Induced__NF-Kappa_B_Pathway_in_Breast_Cancer.pdf

[10] The impact of curcumin on breast cancer – https://www.ncbi.nlm.nih.gov/pubmed/22772921

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

[12] Delphinidin Reduces Cell Proliferation and Induces Apoptosis of Non-Small-Cell Lung Cancer Cells by Targeting EGFR/VEGFR2 Signaling Pathways – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3790876/

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

[14] Epigallocatechin-3-gallate (EGCG) downregulates EGF-induced MMP-9 in breast cancer cells: involvement of integrin receptor alpha5beta1 in the process – https://www.ncbi.nlm.nih.gov/pubmed/21170718

[15] Green tea catechins inhibit angiogenesis through suppression of STAT3 activation – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664280/

[16] The flavonoid fisetin as an anticancer agent targeting the growth signaling pathways – https://www.sciencedirect.com/science/article/pii/S0014299916304319?via%3Dihub

[17] Anti-cancer effects of fisetin on mammary carcinoma cells via regulation of the PI3K/Akt/mTOR pathway: In vitro and in vivo studies – https://www.spandidos-publications.com/10.3892/ijmm.2018.3654

[18] Gallic acid abolishes the EGFR/Src/Akt/Erk-mediated expression of matrix metalloproteinase-9 in MCF-7 breast cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/27087131

[19] Gamma-tocotrienol reversal of epithelial-to-mesenchymal transition in human breast cancer cells is associated with inhibition of canonical Wnt signalling – https://www.ncbi.nlm.nih.gov/pubmed/27323693

[20] Induction of apoptosis and inhibition of c-erbB-2 in MDA-MB-435 cells by genistein – https://www.ncbi.nlm.nih.gov/pubmed/10427135

[21] Genistein exerts multiple suppressive effects on human breast carcinoma cells – https://www.ncbi.nlm.nih.gov/pubmed/9809990

[22] Glycyrrhetinic acid potently suppresses breast cancer invasion and metastasis by impairing the p38 MAPK-AP1 signaling axis – https://www.ncbi.nlm.nih.gov/pubmed/25828376

[23] Molecular Targets of Isothiocyanates in Cancer: Recent Advances – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122603/

[24] Anti-angiogenic and anti-inflammatory properties of kahweol, a coffee diterpene – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153489/

[25] Lupeol, A Novel Anti-inflammatory and Anti-cancer Dietary Triterpene – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2764818/

[26] 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

[27] 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

[28] Effects of a-Mangostin on Viability, Growth and Cohesion of Multicellular Spheroids Derived from Human Breast Cancer Cell Lines – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765736/

[29] 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

[30] Inhibition of human cancer cell growth and metastasis in nude mice by oral intake of modified citrus pectin – https://www.ncbi.nlm.nih.gov/pubmed/12488479

[31] Myricetin suppresses breast cancer metastasis through down-regulating the activity of matrix metalloproteinase (MMP)-2/9 – https://www.ncbi.nlm.nih.gov/pubmed/29532526

[32] 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/

[33] Naringenin prevents TGF-ß1 secretion from breast cancer and suppresses pulmonary metastasis by inhibiting PKC activation – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4818388/

[34] Alkaloids Isolated from Natural Herbs as the Anticancer Agents – https://www.hindawi.com/journals/ecam/2012/485042/

[35] Effects of Psoralen as an Anti-tumor Agent in Human Breast Cancer MCF-7/ADR Cells – https://www.ncbi.nlm.nih.gov/pubmed/26902225

[36] Silibinin induces the generation of nitric oxide in human breast cancer MCF-7 cells – https://www.ncbi.nlm.nih.gov/pubmed/20370556

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

[38] 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

[39] 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

[40] Broccoli and watercress suppress matrix metalloproteinase-9 activity and invasiveness of human MDA-MB-231 breast cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/15953625

[41] Tricin, 4′,5,7-trihydroxy-3′,5′-dimethoxyflavone, exhibits potent antiangiogenic activity in vitro – https://www.ncbi.nlm.nih.gov/pubmed/27498749

[42] Ursolic acid inhibits breast cancer growth by inhibiting proliferation, inducing autophagy and apoptosis, and suppressing inflammatory responses via the PI3K/AKT and NF-kB signaling pathways in vitro – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5639319/

[43] Vanillin suppresses in vitro invasion and in vivo metastasis of mouse breast cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/15854801

[44] Preventive Efficacy of Vanillic Acid on Regulation of Redox Homeostasis, Matrix Metalloproteinases and Cyclin D1 in Rats Bearing Endometrial Carcinoma – https://www.ncbi.nlm.nih.gov/pubmed/29062174

[45] Vitamin D3 decreases glycolysis and invasiveness, and increases cellular stiffness in breast cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/29216499

[46] Dietary Carotenoids and the Risk of Invasive Breast Cancer –

https://www.ncbi.nlm.gov/pmc/articles/PMC3564658/

[47] 2′-Hydroxyflavanone inhibits in vitro and in vivo growth of breast cancer cells by targeting RLIP76 – https://www.ncbi.nlm.nih.gov/pubmed/30136444

[48] Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials – https://www.ncbi.nlm.nih.gov/pubmed/22440947

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