Jesse Mooneyham

Introduction. Cancer is a collection of diseases caused by genetic defects resulting in either the loss of function of tumor suppressor genes or gain of function of oncogenes¹. Increasing evidence suggests that epigenetic modifications of gene expression can play a critical role in tumorigenesis and the progression of cancer^1,2. Dietary phytochemicals have been shown to have chemopreventative properties, but their effects on the epigenome are not well understood. The role of apinenin, curcumin, and green tea polyphenols (GTPs) on the epigenome in tumorigenesis are being investigated as potential therapeutic options. Methods. MDA-MB-231 human breast cancer cells were treated with apigenin and then analyzed using flow cytometry, and immunoprecipitation assays¹. HDAC assays and PCR specific for p21^WAF1/CIP1 were used to determine effect on H3 histone at the p21^WAF1/CIP1 site¹. HT29 human colorectal cancer cells were treated with curcumin and then subjected to analysis via methylation-specific PCR³. Human breast cancer cell lines MDA-MB-231 and MCF-7 were treated with GTPs and analyzed using methylation-specific PCR⁴. Invasive activity was analyzed using gelatin zymography⁴. Results. Cells treated with apigenin showed markedly decreased proliferation in a concentration-dependent manner^1,2. Cells treated with apigenin demonstrated HDAC inhibition and increased expression of p21^WAF1/CIP1. Curcumin-treated cells demonstrated decreased viability of colorectal cancer cells^2,3. Down regulation of many DNMT’s were observed in treated cells and DLEC1 was hypo-methylated compared to control groups^2,3.  Breast cancer cells treated with GTPs demonstrated reduction of class I HDACs and increased expression of TIMPs^2,4. Treated cells showed decreased gelatinolysis compared to control groups⁴. Conclusions. Apigenin exhibits epigenetic effects on cancer by inhibiting HDACs, leading to acetylation of the H3 histone. Acetylation leads to greater expression of p21^WAF1/CIP1 and greater cell cycle arrest in breast cancer cells. Curcumin demonstrated the down-regulation of several DNMTs, leading to hypo-methylation of the DLEC1 gene in colorectal cancer cells, decreasing their viability. GTPs have demonstrated an effect of reducing HDACs, leading to greater expression of TIMPs and decreased migration of breast cancer cells. Studies such as these demonstrate that the role of phytochemicals on the epigenome needs further investigation, but shows promise as potential therapeutic options in cancer treatment.

1. Tseng T, Chien M, Lin W, Wen Y, Chow J, et al. Inhibition of MDA-MB-231 Breast Cancer Cell Proliferation and Tumor Growth by Apigenin Through Induction of G2/M Arrest and Histone H3 Acetylation-mediated p21^WAF1/CIP1 Environ Toxicol. 2017; 32(2): 434-444. [PubMed: 26872304]
2. Shanker E, Kanwai R, Candama M, Gupta S. Dietary phytochemical as epigenetic modifiers in cancer: Promises and challenges. Semin Cancer Biol. 2016; 40-41:82-99 [PubMed: 27117759]
3. Guo Y, Shu L, Zhang C, Su Z, Kong A. Curcumin inhibits anchorage-independent growth of HT29 human colon cancer cells by targeting epigenetic restoration of the tumor suppressor gene DLEC1. Biochem Pharmacol. 2015; 94(2): 69-78. [PubMed: 25640947]
4. Deb G, Thakur V, Limaye A, Gupta S. Epigenetic Induction of Tissue Inhibitor of Matrix Metalloproteinase-3 by Green Tea Polyphenols in Breast Cancer Cells. Molecular Carcinogenesis. 2015; 54: 485-499. [PubMed: 24481780]