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.