Methyl 5-[(1H-indol-3-yl)selanyl]-1H-benzoimidazol-2-ylcarbamate (M-24), a novel tubulin inhibitor, causes G2/M arrest and cell apoptosis by disrupting tubulin polymerization in human cervical and breast cancer cells.

Abstract

Methyl 5-[(1H-indol-3-yl)selanyl]-1H-benzoimidazol-2-ylcarbamate (M-24) is a newly synthesized analogue of nocodazole by our group and has been found to be active for some cancer cells. However, its sensitivity to different cell lines and the underlying anticancer mechanism are still unclear. In this study, we proved that M-24 had strong time- and dose-dependent anti-proliferative effects on human cervical cancer HeLa cells and human breast carcinoma MCF-7 cells. We demonstrated that the growth inhibitory effects of M-24 in both cell lines were associated with microtubule depolymerization. Furthermore, M-24 treatment resulted in cell cycle arrest at the G2/M phase in a dose-dependent manner with subsequent apoptosis induction. Western blotting analysis revealed that up-regulation of cyclin B1 and cdc2 was related with G2/M arrest in both cell lines. In addition, M-24-induced HeLa cell apoptosis was mainly associated with mitochondria-dependent intrinsic pathway. However, M-24-induced MCF-7 cell apoptosis was associated with both mitochondrial and death receptor pathway. In conclusion, M-24 caused apoptosis through disrupting microtubule assembly and inducing cell cycle arrest in HeLa and MCF-7 cells. Therefore, the novel compound M-24 is a promising microtubule-destabilizing agent that has great potential for the therapy of various malignancies especially human cervical and breast cancers.

• Authors: Daiying Zuo, Xuewei Jiang, Mengting Han, Jiwei Shen, Binyue Lang, Qi Guan, Zhaoshi Bai, Chunming Han, Zengqiang Li, Weige Zhang, Yingliang Wu
• Journal: Toxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 42 Pg. 139-149 (Aug 2017) ISSN: 1879-3177 [Electronic] England
• PMID: 28412508 (Publication Type: Journal Article)
• Copyright: Copyright © 2017. Published by Elsevier Ltd.

Chemical References

• Antineoplastic Agents
• Organoselenium Compounds
• Proto-Oncogene Proteins c-bcl-2
• Tubulin
• Tubulin Modulators
• methyl 5-((1H-indol-3-yl)selanyl)-1H-benzoimidazol-2-ylcarbamate
• Caspases
• Nocodazole

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Breast Neoplasms (drug therapy, metabolism)
• Caspases (metabolism)
• Female
• G2 Phase Cell Cycle Checkpoints (drug effects)
• HeLa Cells
• Humans
• MCF-7 Cells
• Nocodazole (analogs & derivatives, pharmacology)
• Organoselenium Compounds (pharmacology)
• Polymerization (drug effects)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Tubulin (metabolism)
• Tubulin Modulators (pharmacology)
• Uterine Cervical Neoplasms (drug therapy, metabolism)