Flavonoids and Other Polyphenols Act as Epigenetic Modifiers in Breast Cancer
Abstract
:1. Introduction
2. Methodology
2.1. Flavonoids
2.2. Worldwide Flavonoid Intake
2.3. Flavonoid/Polyphenol Intake and Incidence of Breast Cancer
3. Epigenetics and Breast Cancer
3.1. Epigenetic Modifiers in Clinical Use
3.2. Epigallocatechin Regulates Tumor Suppressor Genes by Promoter Demethylation
3.3. Genistein and Daidzein Modulates Histone Modifications
3.4. Resveratrol Upregulates ATP2A3 Expression
3.5. Quercetin Modulates BRCA1 Expression Level
4. Conclusions and Further Perspectives
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Dietary Source | mg/100 g Source |
---|---|
Green tea, brewed | 70.20 |
Oolong tea, brewed | 34.48 |
Green tea, brewed (decaffeinated) | 26.05 |
Black tea, brewed | 9.36 |
Pecannut | 2.30 |
Fuji Apple, with skin | 1.93 |
Hazelnut | 1.06 |
Black tea, brewed (decaffeinated) | 1.01 |
Cranberry | 0.97 |
Blackberry | 0.68 |
Raspberry | 0.54 |
Plum | 0.48 |
Red Delicious Apple, without skin | 0.46 |
Pistachio nuts | 0.40 |
Granny Smith Apple, with skin | 0.24 |
Golden Delicious Apple, with skin | 0.19 |
Avocado | 0.15 |
Red Delicious Apple, with skin | 0.13 |
Gala Apple, with skin | 0.11 |
Strawberry | 0.11 |
Dietary Source | Serving | Genistein (mg) | Daidzein (mg) |
---|---|---|---|
Soybeans, mature seeds (boiled) | ½ cup | 26.9 | 26.5 |
Soy protein concentrate, aqueous washed | 3.5 ounces | 52.8 | 38.2 |
Soy protein concentrate, alcohol washed | 3.5 ounces | 5.8 | 5.3 |
Soybeans, dry roasted | 1 ounce | 21.2 | 17.4 |
Soybeans, green, boiled (edamame) | ½ cup | 6.3 | 6.7 |
Miso | ½ cup | 32 | 22.6 |
Soy milk, low-fat | 1 cup | 3.7 | 2.4 |
Tofu, soft | 3 ounces | 10.1 | 8.1 |
Tofu, yogurt | ½ cup | 12.3 | 7.5 |
Tempeh | 3 ounces | 30.7 | 19.3 |
Tempeh, cooked | 3 ounces | 18 | 11.1 |
Soy burger, unprepared | 1 patty | 3.5 | 1.6 |
Soy sausage | 3 links | 6.9 | 3.3 |
Soy cheese, cheddar | 1 ounces | 0.6 | 0.5 |
Dietary Source | mg/100 g Source | Dietary Source | mg/100 g Source |
---|---|---|---|
Elderberry juice | 108.16 | Mustard greens, raw | 8.80 |
Radish leaves, raw | 70.37 | Mizuna (Japanese mustard) | 8.55 |
Chokeberry juice | 68.17 | Arugula, raw | 7.92 |
Wild rocket, raw | 66.19 | Blueberry | 7.67 |
Cilantro leaves, raw | 52.90 | Red leaf lettuce, raw | 7.61 |
Yellow wax hot pepper, raw | 50.63 | Red swiss chard, raw | 7.50 |
Juniper berry, ripe | 46.61 | Rowanberry, raw | 7.40 |
Green juniper berry, unripe | 42.81 | Chokeberry juice | 6.49 |
Red onion, raw | 39.21 | Fig, raw | 5.47 |
Radicchio, raw | 31.51 | Crowberry, raw | 5.45 |
Watercress, raw | 29.99 | Chives, raw | 4.77 |
Hartwort leaves | 29.30 | Acerola, west Indian cherry | 4.74 |
Ancho pepper | 27.60 | Blueberry, frozen | 4.64 |
White onion, pan fried | 26.90 | Cranberry, dried | 4.50 |
Corn poppy leaves | 26.30 | Kale, canned | 4.50 |
Onion, cooked | 24.36 | Bayberry, raw | 4.36 |
Hawthorn leaves, raw | 24.10 | Brussels sprout, cooked | 4.33 |
Nalta jute, raw | 23.53 | Green leaf lettuce, raw | 4.16 |
Currant | 22.85 | Red Delicious Apple, with skin | 3.86 |
Okra, raw | 20.97 | Gala Apple, with skin | 3.80 |
Apple, skin only | 19.36 | Golden Delicious Apple, with skin | 3.69 |
Wild bog whortleberry, frozen | 17.70 | Blackberry, raw | 3.58 |
Sour cherry, powder | 17.44 | Bay leaves | 4.33 |
Sweet potato leaves, raw | 16.94 | Green leaf lettuce, raw | 3.19 |
Juneberry or Saskatoon berry | 16.64 | Concord grape | 3.11 |
Cranberry juice | 16.41 | Bilberry, raw | 3.04 |
Buckwheat | 15.38 | Yellow snap bean, cooked | 3.03 |
Asparagus, cooked | 15.16 | Granny Smith Apple, with skin | 2.54 |
Cranberry, raw | 14.84 | Cranberry sauce, canned | 2.40 |
Asparagus, raw | 13.98 | Fuji Apple, with skin | 2.35 |
Goji berry (wolfberry), dried | 13.60 | Broccoli raab, raw | 2.25 |
Lingonberry (cowberry) | 13.30 | Purple plum, raw | 2.19 |
Spring onion leaves | 12.60 | Tomato juice, canned | 1.19 |
Black diamond plum, with peel | 12.45 | Red grape | 1.04 |
Cranberry bush berry, raw | 10.73 | Watercress, steamed | 0.63 |
Sweet potato leaves, cooked | 9.84 | Golden Delicious Apple, without skin | 0.51 |
Arctic brambleberry | 9.10 | Red Delicious Apple, without skin | 0.41 |
Flavonoid | Epigenetic Modification | Breast Cancer Cell Line | Regulated Genes | Reference |
---|---|---|---|---|
EGCG | ↓ Promotermethylation ↓ H3Lys9 Acetylation | MCF-7 | ↓ hTERT | Berletch et al., 2008 [58] |
EGCG | ↓ DNMT ↓ HAT | MCF-7 & MDA-MB-231 | ↓ hTERT | Meeran et al., 2011 [59] |
EGCG | ↓ Promoter methylation ↓ DNMT | MDA-MB-231 | Signal peptide-CUB-EGF domain-containing protein 2 (SCUBE2) | Lin et al., 2014 [61] Sheng et al., 2019 [62] |
EGCG & SAHA | ↓ DNMT ↑ Histone Acetylation | MCF-7, MDA-MB-231 & MDA-MB-157 | ↑ ERα, p27, & E-cadherin | Lewis et al., 2018 [64] |
EGCG & Sulforaphane | ↓ DNMT& HDAC | HMECs MDA-MB-231 & MDA-MB-157 | ↑ DCBLD2, ↓ SPET9↑ ERα | Li et al., 2016 [63] Li et al., 2017 [66] |
EGCG & Trichostatin A | ↑ Histone Acetylation ↑ H3K4Me2 ↓ H3K9 | MDA-MB-231 | ↑ ERα | Liet al., 2010 [65] |
Genistein & Trichostatin A | ↑ Histone Acetylation ↓ DNMT | MDA-MB-231 | ↑ ERα | Li et al., 2013 [82] |
Genistein and Daidzein | ↓ Promoter methylation ↓ MeCP2 | MDA-MB-231 | ↑ BRCA1 & BRCA2 | Bosviel et al., 2012 [83] |
Genistein | ↓ DNMT1 | UACC-3199 HCC38 | ↑ BRCA1 & ERα | Romagnolo et al., 2017 [84] Donovan et al., 2019 [85] |
Genistein | ↓ H3K27Me3 & H3K9Me3, ↑ H4K8Ac and H3K4Ac | MDA-MB-231 | ↑ EZH2, BRCA1, ERα, ERβ, SRC3 and P300 | Dagdemir et al., 2013 [88] |
Genistein and Sulforaphane | ↓ HDAC & HMT | MCF-7 & MDA-MB-231 | ↓ KLF4 and hTERT | Paul et al., 2018 [89] |
Resveratrol | ↑ H3K27Ac ↓ DNMT, MeCP2 & MBD2 | MDA-MB-231 | ↑ ATP2A3 | Izquierdo-Torres et al., 2019 [94] |
Resveratrol | ↓ DNMT1 | ↑ BRCA1 | Papoutsis et al., 2015 [97] |
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Selvakumar, P.; Badgeley, A.; Murphy, P.; Anwar, H.; Sharma, U.; Lawrence, K.; Lakshmikuttyamma, A. Flavonoids and Other Polyphenols Act as Epigenetic Modifiers in Breast Cancer. Nutrients 2020, 12, 761. https://doi.org/10.3390/nu12030761
Selvakumar P, Badgeley A, Murphy P, Anwar H, Sharma U, Lawrence K, Lakshmikuttyamma A. Flavonoids and Other Polyphenols Act as Epigenetic Modifiers in Breast Cancer. Nutrients. 2020; 12(3):761. https://doi.org/10.3390/nu12030761
Chicago/Turabian StyleSelvakumar, Priyanga, Aja Badgeley, Paige Murphy, Hina Anwar, Urvashi Sharma, Katharine Lawrence, and Ashakumary Lakshmikuttyamma. 2020. "Flavonoids and Other Polyphenols Act as Epigenetic Modifiers in Breast Cancer" Nutrients 12, no. 3: 761. https://doi.org/10.3390/nu12030761