Cantharidic acid induces apoptosis through the p38 MAPK signaling pathway in human hepatocellular carcinoma.

Abstract

Cantharidin analogs exhibit anticancer activities, including apoptosis. However, the molecular mechanisms underlying the effects of cantharidic acid (CA), a cantharidin analog, on apoptosis in hepatocellular carcinoma (HCC) cells are unclear. Thus, in this study, we evaluated the anticancer activities of CA by investigating its ability to trigger apoptosis in SK-Hep-1 cells. Our data demonstrated that CA effectively inhibited the proliferation of SK-Hep-1 cells in a dose-dependent manner. Furthermore, CA effectively triggered cell cycle arrest and induced apoptosis, as determined by flow cytometric analysis. Western blotting revealed that CA significantly activated proapoptotic signaling including caspase-3, -8, and -9 in SK-Hep-1 cells. Moreover, treatment of SK-Hep-1 cells with CA induced the activation of ERK, p38, and c-Jun N-terminal kinase. Moreover, the inhibition of p38 by specific inhibitors abolished CA-induced cell apoptosis. In conclusion, our results indicated that CA induces apoptosis in SK-Hep-1 cells through a p38-mediated apoptotic pathway and could be a new HCC therapeutic agent.

• Authors: I-Che Feng, Ming-Ju Hsieh, Pei-Ni Chen, Yi-Hsien Hsieh, Hsin-Yu Ho, Shun-Fa Yang, Chao-Bin Yeh
• Journal: Environmental toxicology (Environ Toxicol) Vol. 33 Issue 3 Pg. 261-268 (Mar 2018) ISSN: 1522-7278 [Electronic] United States
• PMID: 29159945 (Publication Type: Journal Article)
• Copyright: © 2017 Wiley Periodicals, Inc.

Chemical References

• Antineoplastic Agents
• cantharidic acid
• JNK Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases
• CASP3 protein, human
• Caspase 3
• Caspase 8
• Caspase 9
• Cantharidin

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cantharidin (analogs & derivatives, pharmacology)
• Carcinoma, Hepatocellular (metabolism, pathology)
• Caspase 3 (metabolism)
• Caspase 8 (metabolism)
• Caspase 9 (metabolism)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Enzyme Activation
• Humans
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Liver Neoplasms (metabolism, pathology)
• MAP Kinase Signaling System
• p38 Mitogen-Activated Protein Kinases (metabolism)