MPTOB169, a New Tubulin Inhibitor, Inhibits Cell Growth and Induces G2/M Arrest in Nonresistant and Paclitaxel-Resistant Cancer Cells

作者：Lee Wei Hwa; Liu Hsinjin Eugene; Chang Jang Yang; Liou Jing Ping; Huang Huei Mei^*

来源：Pharmacology, 2013, 92(1-2): 90-98.

DOI：10.1159/000351852

• MPTOB169
• Tubulin inhibitor
• Growth inhibition
• G2/M arrest
• Paclitaxel resistance
• Leukemia cells.
• Lymphoma cells

The polymerization of tubulin molecules forms microtubules which are considered an attractive target for cancer treatment. Herein, we synthesized a new tubulin inhibitor, MPTOB169 (2-dimethylamino-N41-(4-methoxy-benzenesulfonyl)-2,3-di-hydro-1H-indol-7-yl]-acetamide) and demonstrated its action in leukemia cell lines HL60 and NB4 and lymphoma cell line U937. We found that MPTOB169 prevented tubulin assembly by binding the colchicine-binding site of tubulin in vitro. MPTOB169 also induced tubulin depolymerization in vivo. MPTOB169 inhibited the growth of HL60, NB4, and U937 cells in dose- and time-dependent manners. It also inhibited the growth of paclitaxel-resistant cancer cells. In addition, MPTOB169 caused G2/M cell cycle arrest in nonresistant and paclitaxel-resistant cancer cells, with a concomitant increase in cyclin B1 levels and cyclin-dependent kinase 1 (CDK1) phosphorylation. These results suggest that MPTOB169, a tubulin inhibitor, inhibits cell growth and induces G2/M cell cycle arrest of cancer cells through the disruption of tubulin polymerization.

• 出版日期2013
• 单位河北医科大学