title: 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.
abstract: 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.
authors.affiliation: Department of Nutrition, Southwest Hospital, 3rd Military Medical University, Chongqing, China.
authors.forename: Qian-fen
authors.initials: QF
authors.lastname: Gong
authors.forename: E-hu
authors.initials: EH
authors.lastname: Liu
authors.forename: Rong
authors.initials: R
authors.lastname: Xin
authors.forename: Xiuning
authors.initials: X
authors.lastname: Huang
authors.forename: Ning
authors.initials: N
authors.lastname: Gao
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects*; D000071877:Checkpoint Kinase 1; D016889:Endometrial Neoplasms / Q000473:pathology*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D011494:Protein Kinases / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D004958:Estradiol; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1