title: Antiproliferative effects of dehydrocostuslactone through cell cycle arrest and apoptosis in human ovarian cancer SK-OV-3 cells.
abstract: The present study was conducted to investigate the effects of dehydrocostuslactone on the cell cycle distribution and apoptosis of human ovarian cancer SK-OV-3 cells and explored the mechanisms underlying these effects. Dehydrocostuslactone significantly inhibited cell proliferation in a dose-dependent manner and produced significant cell cycle arrest at the G2/M interface when applied at its IC50 (10.7 microM) for this system. Under the same conditions, dehydrocostuslactone caused a slight decrease in the expression of the cell cycle regulatory proteins CDK4 and cyclin E, as well as a small increase in the expression of the cyclin-dependent kinase inhibitor p21Cip1. In addition, the dehydrocostuslactone-induced accumulation of cells at the G2/M phase transition interface resulted in a significant decrease in CDK1 together with cyclin A and cyclin B. This cell cycle arrest induced apoptosis, as confirmed by annexin V and DAPI staining. Following exposure to dehydrocostuslactone, there was a marked increase in the expression of the apoptotic protein Bax and the downstream target p53, a tumor suppressor transcription factor protein, causing the release of cytochrome c. Based on our findings, the mechanism by which dehydrocostuslactone causes cell cycle arrest is via CDK1 down-regulation, and its induction of apoptosis appears to be related to the activation of p53 and the release of cytochrome c.
authors.affiliation: Cancer Research Institute, The Catholic University of Korea, Seocho-gu, Seoul, Republic of Korea.
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Choi
authors.forename: Woong Shick
authors.initials: WS
authors.lastname: Ahn
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D018797:Cell Cycle Proteins; D007783:Lactones; D012717:Sesquiterpenes; C083030:dehydrocostus lactone