title: Anti-proliferative activity and cell cycle arrest induced by evodiamine on paclitaxel-sensitive and -resistant human ovarian cancer cells.
abstract: Chemo-resistance is the main factor for poor prognosis in human ovarian epithelial cancer. Active constituents derived from Chinese medicine with anti-cancer potential might circumvent this obstacle. In our present study, evodiamine (EVO) derived from Evodia rutaecarpa (Juss.) Benth suppressed the proliferation of human epithelial ovarian cancer, A2780 and the related paclitaxel-resistant cell lines and did not cause cytotoxicity, as confirmed by the significant decline of clone formation and the representative alterations of CFDA-SE fluorescence. Meanwhile, EVO induced cell cycle arrest in a dose- and time-dependent manner. This disturbance might be mediated by the cooperation of Cyclin B1 and Cdc2, including the up-regulation of Cyclin B1, p27, and p21, and activation failure of Cdc2 and pRb. MAPK signaling pathway regulation also assisted in this process. Furthermore, chemo-sensitivity potential was enhanced as indicated in A2780/PTX(R) cells by the down-regulation of MDR-1 expression, accompanied by MDR-1 function suppression. Taken together, we confirmed initially that EVO exerted an anti-proliferative effect on human epithelial ovarian cancer cells, A2780/WT and A2780/PTX(R), induced G2/M phase cell cycle arrest, and improved chemo-resistance. Overall, we found that EVO significantly suppressed malignant proliferation in human epithelial ovarian cancer, thus proving to be a potential anti-cancer agent in the future.
authors.affiliation: University of Macau, Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, Macau, China.
authors.forename: Zhang-Feng
authors.initials: ZF
authors.lastname: Zhong
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou, Gansu, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
authors.affiliation: University of Macau, Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, Macau, China.
authors.forename: Sheng-Peng
authors.initials: SP
authors.lastname: Wang
authors.affiliation: Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Wen-An
authors.initials: WA
authors.lastname: Qiang
authors.affiliation: University of Macau, Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, Macau, China.
authors.forename: Yi-Tao
authors.initials: YT
authors.lastname: Wang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000077216:Carcinoma, Ovarian Epithelial; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D051379:Mice; D009375:Neoplasms, Glandular and Epithelial; D010051:Ovarian Neoplasms; D017239:Paclitaxel / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011799:Quinazolines; C049639:evodiamine; D017239:Paclitaxel