Brusatol inhibits growth and induces apoptosis in pancreatic cancer cells via JNK/p38 MAPK/NF-κb/Stat3/Bcl-2 signaling pathway.

Abstract

Brusatol, isolated from brucea, has been proved to exhibit anticancer influence on various kind of human malignancies. However, the role that brusatol plays in pancreatic cancer is seldom known by the public. Through researches brusatol was proved to inhibit growth and induce apoptosis in both PATU-8988 and PANC-1 cells by decreasing the expression level of Bcl-2 and increasing the expression levels of Bax, Cleaved Caspase-3. Then we found the activation of the JNK, p38 MAPK and inactivation of the NF-κb, Stat3 are related with the potential pro-apoptotic signaling pathways. However, SP600125 could not only abrogated the JNK activation caused by brusatol, but also reverse the p38 activation and the decrease of Bcl-2 as SB203580 did. Besides, SP600125 and SB203580 also reversed the inactivation of NF-κb and Stat3. Furthermore, BAY 11-7082 and S3I-201 indeed had the similar effect as brusatol had on the expression of Phospho-Stat3 and Bcl-2. To sum up, we came to a conclusion that in pancreatic cancer, brusatol do inhibit growth and induce apoptosis. And we inferred that brusatol illustrates anticancer attribution via JNK/p38 MAPK/NF-κb/Stat3/Bcl-2 signaling pathway.

• Authors: Yukai Xiang, Wen Ye, Chaohao Huang, Bin Lou, Jie Zhang, Dinglai Yu, Xince Huang, Bicheng Chen, Mengtao Zhou
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 487 Issue 4 Pg. 820-826 (06 10 2017) ISSN: 1090-2104 [Electronic] United States
• PMID: 28455228 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017. Published by Elsevier Inc.

Chemical References

• Antineoplastic Agents
• NF-kappa B
• Proto-Oncogene Proteins c-bcl-2
• Quassins
• STAT3 Transcription Factor
• brusatol
• JNK Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases

Topics

• Antineoplastic Agents (administration & dosage, pharmacology)
• Apoptosis (drug effects)
• Cell Proliferation (drug effects)
• Humans
• JNK Mitogen-Activated Protein Kinases (metabolism)
• MAP Kinase Signaling System (drug effects)
• NF-kappa B (metabolism)
• Pancreatic Neoplasms (drug therapy, metabolism, pathology)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Quassins (administration & dosage, pharmacology)
• STAT3 Transcription Factor (metabolism)
• Tumor Cells, Cultured
• p38 Mitogen-Activated Protein Kinases (metabolism)