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
| Autor: | Feng‑Xia Liu, Lin Qu, Xiaohong Yang, Qiao Xiao, Kai‑Qun Ren, Xiao‑Cheng Cao |
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| Rok vydání: | 2014 |
| Předmět: |
chemistry.chemical_classification
reactive oxygen species Cancer Research Reactive oxygen species Programmed cell death Kinase c-jun apoptosis General Medicine Articles Biology Cell biology chemistry.chemical_compound Immunology and Microbiology (miscellaneous) chemistry colon cancer Apoptosis casticin Cancer cell Casticin ASK1 Bim apoptosis signal-regulating kinase 1 c-Jun N-terminal kinase |
| Zdroj: | Experimental and Therapeutic Medicine |
| ISSN: | 1792-0981 |
| Popis: | Casticin is one of the main components of the fruits of Vitex rotundifolia L. 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. |
| Databáze: | OpenAIRE |
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