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.
Highlights
Ovarian cancer is the tenth most common cancer and the fifth leading cause of cancer death among women in the United States [1]
We have previously reported that TF3 inhibited human ovarian cancer cells by inducing apoptosis and cell cycle arrest [23] and by suppressing angiogenesis [24]
We investigated whether TF3 could potentiate the inhibitory effect of cisplatin against human ovarian cancer cell lines
Summary
Ovarian cancer is the tenth most common cancer and the fifth leading cause of cancer death among women in the United States [1]. Ovarian cancer causes a higher death rate than any other gynecologic cancer, leading to approximately 5% of cancer deaths among women. The conventional treatment for advanced ovarian cancer is surgical resection of the tumor mass followed by platinum based-chemotherapy [2]. Most patients with advanced ovarian cancer respond well to the first-line conventional treatment, 70% of the patients relapse within 18 months of the treatment [3]. The used chemotherapeutic agents often become ineffective to relapsing patients. The high relapse rate and drug resistance lead to low long-term survival rate (less than 40%) of patients with advanced ovarian cancer [4]
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