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新型化合物 JBIR-23 诱导恶性间皮瘤细胞的微管聚合和凋亡。

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

机构信息

Biomedicinal Information Research Center, National Institute of Advanced Industrial Science and Technology, Aomi, Koto-ku, Tokyo, Japan.

出版信息

Cancer Lett. 2011 Jan 28;300(2):189-96. doi: 10.1016/j.canlet.2010.10.005. Epub 2010 Nov 4.

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.

摘要

恶性胸膜间皮瘤(MPM)是一种侵袭性强、预后差的肿瘤。因此,需要开发新的治疗药物来治疗它。我们最近报道了从链霉菌 AK-AB27 中分离出一种新型抗 MPM 化合物,命名为 JBIR-23。在这项研究中,JBIR-23 通过促进微管蛋白聚合和 G₂/M 期阻滞发挥其对 MPM 细胞的细胞毒性作用,随后通过 caspase 途径诱导细胞凋亡,这是通过磷酸化 p38 丝裂原活化蛋白激酶和 c-jun N 端激酶实现的。此外,体内分析表明,JBIR-23 可防止荷瘤裸鼠的肿瘤生长,且无明显副作用。

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