期刊
CANCER BIOLOGY & THERAPY
卷 6, 期 5, 页码 787-794出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cbt.6.5.4006
关键词
BM6; Vinca alkaloids; anti-tumor; mitotic arrest; cytoskeleton; tubulin binding; pharmacokinetics
类别
The aim of this study was to evaluate the anti-tumor activities and to establish the mechanism of the action of 3-decarboxyl-acetyloxylmethyl-anhydrovinblastine (BM6), a new semi-synthetic Vinca alkaloid, in an effort towards finding the favorable therapeutics of Vinca alkaloid derivatives. BM6 was characterized by its superior in vivo activity to vinorelbine in preclinical tumor models, though BM6 exerted in vitro cytotoxic activity against a wide spectrum of tumor cell lines with IC50 values generally 10-fold higher than the classic Vinca alkaloids. Of note, BM6 displayed more potent cytotoxic activity against multidrug-resistant sublines. We further found that BM6 shared the mitotic arresting and tubulin-interacting properties comparable with other Vinca alkaloids. BM6 also induced significant cell cycle arrested in mitosis and cytoskeleton disruption via interacting with the Vinca binding site on tubulin. Encouragingly, the features in term of its higher tubulin binding affinities and better pharmacokinetic profiles highlight BM6 distinct from other Vinca alkaloids, which help provide more data for exploiting new semi-synthetic Vinca alkaloids.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据