Progesterone induces apoptosis and up-regulation of p53 expression in human ovarian carcinoma cell lines

Abstract

METHODS. Antiproliferation effects of PROG on 3AO and AO ovarian carcinomaShanghai Institute of Cell Biology, Chinese cells were determined by 3 H-thymidine incorporation. Apoptosis of the PROGAcademy of Sciences, Shanghai, China. treated cells was determined by DNA laddering analysis and was quantitated by both nuclear condensation and flow cytometry after cells were stained with propidium iodide. Cell cycle analysis was also performed by flow cytometry. The expression of p53, bcl-2, and c-myc after 72 hours of PROG treatment was detected by Northern blot analysis. RESULTS. In both 3AO and AO cell lines, cells proliferation was maximally inhibitedby PROG after 72 hours of treatment at 10 mM concentration. Under the same conditions, more than 50% of PROG-treated cells had undergone apoptosis, whereas less than 3% of the cells were apoptotic in untreated cell cultures. After exposure to PROG for 72 hours, cells were arrested in the G 1 phase of the cell cycle, and the levels of p53 mRNA were remarkably increased in both cell lines.No changes in expression of bcl-2 or c-myc were detected.CONCLUSIONS. PROG significantly inhibited cell proliferation and induced apoptosis in both of the ovarian carcinoma cell lines tested in this study. PROG treatment markedly up-regulated p53 expression in these cells, indicating involvement of p53 in PROG-induced apoptosis.

Gender of Offspring and Maternal Risk of Invasive Epithelial Ovarian Cancer

“…In humans, circulating androstenedione was found to be positively associated with ovarian cancer risk (32). Several experimental studies indicate a protective effect for progesterone on ovarian carcinogenesis through apoptotic mechanisms (35)(36)(37).…”

Progesterone Inhibits the Growth of Human Neuroblastoma: In Vitro and In Vivo Evidence

“…in vitro and in vivo (6)(7)(8)(9). Taken together, these facts suggest ways in which natural P4 might function as a chemotherapeutic agent against neurogenic tumors such as neuroblastoma.…”

Identification of ATF-3, caveolin-1, DLC-1, and NM23-H2 as putative antitumorigenic, progesterone-regulated genes for ovarian cancer cells by gene profiling

“…A handful of studies have demonstrated that progestins inhibit cell growth and/or induce apoptosis in OCa cell cultures (Bu et al, 1997;Hu and Deng, 2000;Keith and Bonavida, 2001;Yu et al, 2001;Syed and Ho, 2003). Alterations in apoptosis regulators such as bcl-2, c-myc, and p53 were detected in OCa cells undergoing progestin-induced apoptosis (Bu et al, 1997;Hu and Deng, 2000;Athanassiadou et al, 1998). Relatively high doses of progestins (1 mM range) were used in these studies to achieve growth inhibition and apoptosis.…”