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Int. J. Mol. Sci. 2018, 19(1), 117; https://doi.org/10.3390/ijms19010117

Theaflavin-3,3′-Digallate Enhances the Inhibitory Effect of Cisplatin by Regulating the Copper Transporter 1 and Glutathione in Human Ovarian Cancer Cells

1
Department of Tea Science, Zhejiang University, Hangzhou 310058, China
2
College of Science, Technology and Mathematics, Alderson Broaddus University, Philippi, WV 26416, USA
3
Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA
4
Department of Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506, USA
*
Authors to whom correspondence should be addressed.
Received: 4 December 2017 / Revised: 24 December 2017 / Accepted: 29 December 2017 / Published: 2 January 2018
(This article belongs to the Special Issue Molecular Research on Urology)
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Abstract

Ovarian cancer has the highest fatality rate among the gynecologic cancers. The side effects, high relapse rate, and drug resistance lead to low long-term survival rate (less than 40%) of patients with advanced ovarian cancer. Theaflavin-3,3′-digallate (TF3), a black tea polyphenol, showed less cytotoxicity to normal ovarian cells than ovarian cancer cells. We aimed to investigate whether TF3 could potentiate the inhibitory effect of cisplatin against human ovarian cancer cell lines. In the present study, combined treatment with TF3 and cisplatin showed a synergistic cytotoxicity against A2780/CP70 and OVCAR3 cells. Treatment with TF3 could increase the intracellular accumulation of platinum (Pt) and DNA-Pt adducts and enhanced DNA damage induced by cisplatin in both cells. Treatment with TF3 decreased the glutathione (GSH) levels and upregulated the protein levels of the copper transporter 1 (CTR1) in both cells, which led to the enhanced sensitivity of both ovarian cancer cells to cisplatin. The results imply that TF3 might be used as an adjuvant to potentiate the inhibitory effect of cisplatin against advanced ovarian cancer. View Full-Text
Keywords: theaflavin-3,3′-digallate; cisplatin; ovarian cancer; copper transporter 1; glutathione theaflavin-3,3′-digallate; cisplatin; ovarian cancer; copper transporter 1; glutathione
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Pan, H.; Kim, E.; Rankin, G.O.; Rojanasakul, Y.; Tu, Y.; Chen, Y.C. Theaflavin-3,3′-Digallate Enhances the Inhibitory Effect of Cisplatin by Regulating the Copper Transporter 1 and Glutathione in Human Ovarian Cancer Cells. Int. J. Mol. Sci. 2018, 19, 117.

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