Abstract
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.
Highlights
Colorectal cancer (CRC) is one of the leading causes of cancer mortality in the world
These results suggest that casticin causes intracellular reactive oxygen species (ROS) generation, and the oxidative stress further contributed to apoptosis of the human colon cancer HT‐29 cells
The present study examined the apoptotic mechanism of a potential chemopreventive agent, casticin, which is an active ingredient of Fructus Viticis that has been widely used as an anti‐inflammatory drug in Traditional Chinese Medicine for thousands of years [4]
Summary
Colorectal cancer (CRC) is one of the leading causes of cancer mortality in the world. A number of studies have shown that casticin inhibits the growth of various cancer cells, including breast [5], lung [6] and colon cancer [7,8]. Our previous studies demonstrated that casticin induced apoptotic cell death of cervical cancer and hepatocellular carcinoma cells [9,10,11], even without functional p53. Investigations into the apoptosis‐inducing effects and the underlying molecular mechanisms of casticin in p53‐mutated human colon cancer cell lines are required. ASK1 has been reported to be activated by a number of stress signals, including ROS, tumor necrosis factor‐α and endoplasmic reticulum (ER) stress [16,17]. We previously showed that casticin induced apoptotic cell death of cervical cancer cells through the ROS‐dependent activation of JNK [11]. The anti‐carcinogenic effects of casticin on human colon cancer were investigated
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
