title: Induction of apoptosis by casticin in cervical cancer cells: reactive oxygen species-dependent sustained activation of Jun N-terminal kinase.
abstract: Casticin, a polymethoxyflavone from Fructus viticis used as an anti-inflammatory agent in Chinese traditional medicine, has been reported to have anti-cancer activity. The purpose of this study was to examine the apoptotic activity of casticin on human cervical cancer cells and its molecular mechanism. We revealed a novel mechanism by which casticin-induced apoptosis occurs and showed for the first time that the apoptosis induced by casticin is mediated through generation of reactive oxygen species (ROS) and sustained activation of c-Jun N-terminal kinase (JNK) in HeLa cells. Casticin markedly increased the levels of intracellular ROS and induced the expression of phosphorylated JNK and c-Jun protein. Pre-treatment with N-acetylcysteine and SP600125 effectively attenuated induction of apoptosis by casticin in HeLa cells. Moreover, casticin induced ROS production and apoptotic cell death in other cervical cancer cell lines, such as CasKi and SiHa. Importantly, casticin did not cause generation of ROS or induction of apoptosis in normal human peripheral blood mononuclear cells and embryonic kidney epithelium 293 cells. These results suggest that ROS generation and sustained JNK activation by casticin play a role in casticin-induced apoptosis and raise the possibility that treatment with casticin might be promising as a new therapy against human cervical cancer.
authors.affiliation: Department of Gynaecology and Obstetrics, First Affiliated Hospital of University of South China, Hengyang, China.
authors.forename: Fanxiang
authors.initials: F
authors.lastname: Zeng
authors.forename: Li
authors.initials: L
authors.lastname: Tian
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Jianguo
authors.initials: J
authors.lastname: Cao
authors.forename: Meifang
authors.initials: M
authors.lastname: Quan
authors.forename: Xifeng
authors.initials: X
authors.lastname: Sheng
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D005419:Flavonoids; D016755:Proto-Oncogene Proteins c-jun; D017382:Reactive Oxygen Species; C054133:casticin; D048031:JNK Mitogen-Activated Protein Kinases