Abstract
Theaflavin-3,3′-digallate (TF3) is a unique polyphenol in black tea. Epidemiological studies have proved that black tea consumption decreases the incidence rate of ovarian cancer. Our former research demonstrated that TF3 inhibited human ovarian cancer cells. Nevertheless, the roles of checkpoint kinase 2 (Chk2) and p27 kip1 (p27) in TF3-mediated inhibition of human ovarian cancer cells have not yet been investigated. In the current study, TF3 enhanced the phosphorylation of Chk2 to modulate the ratio of pro/anti-apoptotic Bcl-2 family proteins to initiate intrinsic apoptosis in a p53-independent manner and increased the expression of death receptors to activate extrinsic apoptosis in OVCAR-3 human ovarian carcinoma cells. In addition, TF3 up-regulated the expression of p27 to induce G0/G1 cell cycle arrest in OVCAR-3 cells. Our study indicated that Chk2 and p27 were vital anticancer targets of TF3 and provided more evidence that TF3 might be a potent agent to be applied as adjuvant treatment for ovarian cancer.
Highlights
Ovarian cancer is the fifth most deadly cancer in women—an estimated 22,240 new cases of ovarian cancer are expected in the United States in 2018, with an estimated 14,070 deaths [1]
Cells describes the orchestrated collapse of a cell characterized by membrane blebbing, cell shrinkage, The stimulation of apoptosis is a mechanism shared by most chemotherapeutic agents
Our results suggested that p53 might not be a prerequisite for TF3-induced apoptosis and TF3 had the potential to be applied in cancer treatment for sensitizing p53-mutant cancer cells to apoptosis
Summary
Ovarian cancer is the fifth most deadly cancer in women—an estimated 22,240 new cases of ovarian cancer are expected in the United States in 2018, with an estimated 14,070 deaths [1]. Polyphenols, a class of chemicals characterized by the presence of large multiples of phenol structural units, are regarded as potential anticancer candidates because they have multiple molecular targets, high efficiency and little adverse side effects [4]. Epidemiological studies have shown that black tea consumption reduces ovarian cancer risk [5]. (p27) were involved in TF3-mediated inhibition of human ovarian cancer cells was investigated. Theaflavin-3,30 -digallate (TF3) selectively reduced the viability of ovarian cancer cells. * p < 0.05 human immortalized ovarian surface epithelial cells (IOSE 364) cells exposed to TF3.
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