Induction of tubulin polymerization and apoptosis in malignant mesothelioma cells by a new compound JBIR-23.
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.
Biomedicinal Information Research Center, National Institute of Advanced Industrial Science and Technology, Aomi, Koto-ku, Tokyo, Japan.
Ji-Hwan
JH
Hwang
Motoki
M
Takagi
Hideki
H
Murakami
Yoshitaka
Y
Sekido
Kazuo
K
Shin-ya
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001572:Benzofurans / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D008654:Mesothelioma / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D014404:Tubulin / Q000187:drug effects*; D050257:Tubulin Modulators / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D001572:Benzofurans; C538842:JBIR-23; D014404:Tubulin; D050257:Tubulin Modulators