Glochidiol, a natural triterpenoid, exerts its anti-cancer effects by targeting the colchicine binding site of tubulin

被引：5

作者：

Chen, Hongjie ^{[1
]}

Miao, Lijun ^{[1
]}

Huang, Fengxiang ^{[1
]}

Yu, Yali ^{[1
]}

Peng, Qiang ^{[1
]}

Liu, Ying ^{[1
]}

Li, Xixi ^{[1
]}

Liu, Hong ^{[1
]}

机构：

[1] Zhengzhou Univ, Affiliated Hosp 1, Dept Resp & Crit Care Med, Zhengzhou 450052, Henan, Peoples R China

来源：

INVESTIGATIONAL NEW DRUGS | 2021年 / 39卷 / 02期

关键词：

Glochidiol; Lung cancer; Colchicine binding site; HCC-44 Xenograft tumor; CANCER;

D O I：

10.1007/s10637-020-01013-1

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Glochidiol has been shown to have potentially antiproliferative activityin vitro, however its anticancer mechanisms specifically against lung cancer remain unknown. This study aimed to investigate the anti-lung cancer effects of glochidiol in HCC-44 cellsin vitroandin vivo. In the present study, glochidiol was found to have potent antiproliferative activity against lung cancer cell lines NCI-H2087, HOP-62, NCI-H520, HCC-44, HARA, EPLC-272H, NCI-H3122, COR-L105 and Calu-6 with IC(50)values of 4.12 mu M, 2.01 mu M, 7.53 mu M, 1.62 mu M, 4.79 mu M, 7.69 mu M, 2.36 mu M, 6.07 mu M and 2.10 mu M, respectively.In vivo, glochidiol was found to effectively inhibit lung cancer HCC-44 xenograft tumor growth in nude mice. Docking analysis found that glochidiol forms hydrogen bonds with residues of tubulin. Glochidiol was also found to inhibit tubulin polymerizationin vitrowith an IC(50)value of 2.76 mu M. Immunofluorescence staining and EBI competition assay suggest that glochidiol may interact with tubulin by targeting the colchicine binding site. Thus, glochidiol might be a novel colchicine binding site inhibitor with the potential to treat lung cancer.

引用

页码：578 / 586

页数：9