Dietary phenols influence on breast cancer progression through Epigenetic and mechanistic Modifications

Catherine Fergie

Introduction. Breast cancer is the most frequently diagnosed cancer in women throughout the world and is the second most fatal form of cancer amongst women, due to its dangerous nature of tumor metastasis 1,2. Approximately 15-20% of patients have triple negative breast cancer (TNBC), meaning their cell type does not express estrogen receptors, progesterone receptors, or the HER2 oncogene. 1 TNBCs are very invasive cell lines and are associated with chemotherapy resistance, making this type of breast cancer very difficult to treat. 1 Epigenetics is a field of research focused on the non-inherited changes resulting in phenotypic changes without the modification of the DNA sequence itself 3. These changes can be directly involved with the progression of various cancer types 3. Dietary phenols are phytochemicals derived from plants that have been reported to inhibit cancer progression by modifying important routes of tumor growth, development, and metastasis.4 Green Tea Polyphenols (GTP), Epigallocatechin 3-Gallate (EGCG), and Resveratrol (Res) are three of these dietary phenols that have demonstrated abilities to inhibit breast cancer tumor progression and metastasis.2,5,6 Methods.  To determine the effectiveness of GTP and EGCG to increase TIMP-3 production in breast cancer cells, one study treated the breast cancer cell lines MCF-7 and MDA-MB-231 with 20 mM EGCG and 10 mg/mL GTP for 72 hours. 2 Intensity of TIMP-3 was measured after the 72-hour incubation period in both cell lines.2 A different study used breast cancer cell lines MDA-MB-231 and MDA-MB-468, both lines were serum starved and pretreated with 25 μM of Res for 1 hr. and stimulated with  5 μM of lysophosphatidic acid (LPA) and 100ngml−1 of epidermal growth factor (EGF) for 2 hrs. and 0.5 hrs. 6 Immunoblotting and immunofluorescence was performed to quantify phosphorylated-YAP.6 Results. In the study researching EGCG and GTP effects on MCF-7 and MDA-MB-231 cell lines, results showed significant increases in TIMP-3 in both cell lines with both EGCG and GTP. 2 For the research on Res, results showed significant increase in phosphorylated-YAP, even in the presence of LPA and EGF. 6 Conclusions.  EGCG and GTP can inhibit ECM degradation by increasing the quantity of TIMP-3 and Res can halt tumor progression by keeping YAP phosphorylated.2,6 Further research is warranted in the area of dietary phenols because they are sources of low-cost treatment options and can play a role in other cancers and disease processes.4

  1. Giró-Perafita A, Rabionet M, Planas M, et al. EGCG-Derivative G28 Shows High Efficacy Inhibiting the Mammosphere-Forming Capacity of Sensitive and Resistant TNBC Models. Molecules. 2019;24(6):1027. doi:10.3390/molecules24061027
  2. Deb G, Thakur VS, Limaye AM, Gupta S. Epigenetic induction of tissue inhibitor of matrix metalloproteinase-3 by green tea polyphenols in breast cancer cells. Molecular Carcinogenesis. 2014;54(6):485-499. doi:10.1002/mc.22121
  3. Gao Y, Tollefsbol T. Combinational Proanthocyanidins and Resveratrol Synergistically Inhibit Human Breast Cancer Cells and Impact Epigenetic–Mediating Machinery. International Journal of Molecular Sciences. 2018;19(8):2204. doi:10.3390/ijms19082204
  4. Das B, Sarkar N, Bishayee A, Sinha D. Dietary phytochemicals in the regulation of epithelial to mesenchymal transition and associated enzymes: A promising anticancer therapeutic approach. Seminars in Cancer Biology. November 2018:1-23. doi:10.1016/j.semcancer.2018.11.007.
  5. Hao-Feng Gu, Xue-Ying Mao & Min Du (2019): Prevention of breast cancer by dietary polyphenols—role of cancer stem cells, Critical Reviews in Food Science and Nutrition, DOI: 10.1080/10408398.2018.1551778
  6. Kim YN, Choe SR, Cho KH, et al. Resveratrol suppresses breast cancer cell invasion by inactivating a RhoA/YAP signaling axis. Experimental & Molecular Medicine. 2017;49(2). doi:10.1038/emm.2016.151