Induction of tubulin polymerization and apoptosis in malignant mesothelioma cells by a new compound JBIR-23.

Abstract

Malignant pleural mesothelioma (MPM) is a highly aggressive tumor with a poor prognosis. Thus, novel therapeutic agents need to be developed for treating it. We recently reported the isolation of the novel anti-MPM compound designated as JBIR-23 from Streptomyces sp. AK-AB27. In this study, JBIR-23 exerted its cytotoxic effect on MPM cells by promotion of tubulin polymerization and G₂/M arrest, which was followed by apoptosis induction via the caspase pathway through phosphorylation of p38 mitogen-activated protein kinase and c-jun N-terminal kinase. Furthermore, in vivo analysis demonstrated that JBIR-23 prevented tumor growth in tumor-bearing nude mice without evident side effects.

• Authors: Ji-Hwan Hwang, Motoki Takagi, Hideki Murakami, Yoshitaka Sekido, Kazuo Shin-ya
• Journal: Cancer letters (Cancer Lett) Vol. 300 Issue 2 Pg. 189-96 (Jan 28 2011) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 21055871 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Benzofurans
• JBIR-23
• Tubulin
• Tubulin Modulators

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Benzofurans (pharmacology)
• Cell Line, Tumor
• Cell Separation
• Female
• Flow Cytometry
• Humans
• Immunoblotting
• Mesothelioma (drug therapy)
• Mice
• Mice, Nude
• Tubulin (drug effects)
• Tubulin Modulators (pharmacology)
• Xenograft Model Antitumor Assays