Theaflavin-Containing Black Tea Extract: A Potential DNA Methyltransferase Inhibitor in Human Colon Cancer Cells and Ehrlich Ascites Carcinoma-Induced Solid Tumors in Mice

Abstract

Tea is the most popularly consumed beverage in the world. Theaflavin and thearubigins are the key bioactive compounds of black tea that have anticarcinogenic properties as reported in several studies. However, the epigenetic potential of these compounds has not yet been explored. DNA methyltransferase (DNMT) enzymes induce methylation of DNA at cytosine residues and play a significant role in epigenetic regulation and cancer therapy. The present study has explored the role of black tea as a DNMT inhibitor in the prevention of cancer. Herein, the effect of theaflavin has been studied in colon cancer cell line (HCT-116) and EAC-induced solid tumors in mice. It was found that theaflavin prevented cell proliferation and inhibited tumor progression as well. In silico study showed that theaflavin interacted with DNMT1 and DNMT3a enzymes and blocked their activity. Theaflavin also decreased DNMT activity In Vitro and In Vivo as evident from the DNMT activity assay. Results of immunohistochemistry revealed that theaflavin reduced DNMT expression in the tumors of mice. Taken together, our findings showed that theaflavin has a potential role as a DNMT inhibitor in HCT-116 cell line and EAC induced solid tumors in mice.

Acknowledgments

Authors acknowledge the extended support from Dr. Ashish Kumar, former research scholar, CSIR-Indian Institute of Chemical Biology and Ms. Dishari Das Gupta, Research Fellow, Department of Environmental Science, University of Calcutta, for the present work.

Author’s Contribution

Extraction of bioactive compound from tea and its characterization was done by R.B, A.K.G, A.K.A.M and AM; In Vitro cell line studies by R.B; In silico studies (designing and analysis) by S.B, In Vivo studies by R.C and R.B, supervised by U.C. All authors analyzed, interpreted data and wrote draft M.S for respective sections. The entire work has been supervised by P.B.

Disclosure Statement

The authors declare no conflicts of interest.

Ethical Approval

This study was conducted with the approval of the Institutional Ethical Standards Committee.

Funding

This work was supported by the National Tea Research Foundation (175/2015); for funding the project to the Principal investigator, PB; INSA (Indian National Science Academy, New Delhi) Senior scientist position to AKG (INSASP/SS/2018/300) and UGC-UPE fellowship (UGC/340/JRF-UPE II) to RB.