title: Activation of the apoptosis signal-regulating kinase 1/c-Jun N-terminal kinase pathway is involved in the casticin-induced apoptosis of colon cancer cells.
abstract: Casticin is one of the main components of the fruits ofVitex rotundifoliaL. Studies have shown that casticin inhibits the growth of various cancer cells, including colon cancer. In the present study, the anti-carcinogenic effects of casticin on human colon cancer and the underlying mechanisms were investigated. The results revealed that casticin significantly induced apoptosis of HT-29, HCT-116, SW480 and Caco-2 cells, induced the accumulation of reactive oxygen species (ROS) and increased the protein levels of apoptosis signal-regulating kinase 1 (ASK1), c-Jun N-terminal kinase (JNK) and B-cell lymphoma 2-interacting mediator of cell death (Bim) in HT-29 cells. Pretreatment with N-acetylcysteine, an antioxidant chemical compound, inhibited the activation of ASK1, JNK and Bim, as well as the apoptosis induced by casticin. Small interfering RNA targeting ASK1 significantly attenuated the induction of JNK and Bim activation and apoptotic cell death by casticin treatment. SP600125, a specific JNK inhibitor, attenuated Bim activation and apoptosis, but did not alter ASK1 phosphorylation levels. In addition, casticin treatment resulted in apoptosis by the same mechanism in HCT-116, SW480 and Caco-2 cells. These results suggest that casticin significantly induced apoptosis by the activation of the ASK1-JNK-Bim signaling cascade and the accumulation of ROS in colon cancer cells.
authors.affiliation: Department of Examination, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Qu
authors.affiliation: Department of Examination, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Feng-Xia
authors.initials: FX
authors.lastname: Liu
authors.affiliation: Laboratory of Medicine, Medical College, Hunan Normal University, Changsha, Hunan 410016, P.R. China.
authors.forename: Xiao-Cheng
authors.initials: XC
authors.lastname: Cao
authors.affiliation: Laboratory of Medicine, Medical College, Hunan Normal University, Changsha, Hunan 410016, P.R. China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: Laboratory of Medicine, Medical College, Hunan Normal University, Changsha, Hunan 410016, P.R. China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Laboratory of Medicine, Medical College, Hunan Normal University, Changsha, Hunan 410016, P.R. China.
authors.forename: Kai-Qun
authors.initials: KQ
authors.lastname: Ren
keywords: Bim; apoptosis; apoptosis signal-regulating kinase 1; c-Jun N-terminal kinase; casticin; colon cancer; reactive oxygen species