Antiproliferative effects of dehydrocostuslactone through cell cycle arrest and apoptosis in human ovarian cancer SK-OV-3 cells.
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.
Choi
Eun Jeong
EJ
Cancer Research Institute, The Catholic University of Korea, Seocho-gu, Seoul, Republic of Korea.
Ahn
Woong Shick
WS
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*
D018797:Cell Cycle Proteins; D007783:Lactones; D012717:Sesquiterpenes; C083030:dehydrocostus lactone