2ME and 2OHE2 exhibit growth inhibitory effects and cell cycle arrest at G2/M in RL95-2 human endometrial cancer cells through activation of p53 and Chk1.

摘要

Evidence is accumulating that estradiol (E2) may play a dual role in carcinogenic and anticarcinogenic effects by different metabolic pathways. It has been shown that some metabolites of E2 exert proliferative and others anti-proliferative properties on human cancer cells. In the present study, the effects of E2 and its four primary metabolites including 2-hydroxyestradiol (2OHE2), 4-hydroxyestradiol (4OHE2), 2-methoxyestradiol (2ME), and 4-methoxyestradiol (4ME) on proliferation and cell cycle in RL95-2 human endometrial cells were investigated. Our results indicate that 2ME and 2OHE2, but not E2, 4ME, and 4OHE2, exhibit the inhibitory effect through cell cycle arrest at G2/M. 2ME and 2OHE2-induced G2/M cell cycle arrest associated with activation of p53 (Ser15), upregulation of p21(WAF1/Cip1) (p21) and GADD45, inactivation of Cdc2 (Tyr15), as well as downregulation of Cyclin B1. 2ME and 2OHE2-mediated cell cycle arrest at G2/M was also related to activation of protein kinase Chk1 which is associated with p53 (Ser20) activation and downstream responses.