Journal
MOLECULES
Volume 24, Issue 4, Pages -Publisher
MDPI
DOI: 10.3390/molecules24040673
Keywords
theaflavin-3; 3-digallate; apoptosis; death receptors; Chk2; cell cycle arrest; p27
Funding
- National Institutes of Health (NIH) from the National Center for Research Resources [P20RR016477]
- National Institute for General Medical Sciences (NIGMS) [P20GM103434]
- NIGMS, a component of the NIH [P20GM104932]
- COBRE grant [GM102488/RR032138]
- ARIA S10 grant [RR020866]
- FORTESSA S10 grant [OD016165]
- INBRE grant [GM103434]
- China Postdoctoral Science Foundation [2017M611065]
- Zhejiang Province Postdoctoral Science Grant
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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.
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