MPT0B169, a new tubulin inhibitor, inhibits cell growth and induces G2/M Arrest in nonresistant and paclitaxel-resistant cancer cells

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Abstract

The polymerization of tubulin molecules forms microtubules which are considered an attractive target for cancer treatment. Herein, we synthesized a new tubulin inhibitor, MPT0B169 (2-dimethylamino-N-[1-(4-methoxy- benzenesulfonyl)-2, 3-dihydro-1H-indol-7-yl]-acetamide) and demonstrated its action in leukemia cell lines HL60 and NB4 and lymphoma cell line U937. We found that MPT0B169 prevented tubulin assembly by binding the colchicine-binding site of tubulin in vitro. MPT0B169 also induced tubulin depolymerization in vivo. MPT0B169 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, MPT0B169 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 MPT0B169, a tubulin inhibitor, inhibits cell growth and induces G2/M cell cycle arrest of cancer cells through the disruption of tubulin polymerization.

Original languageEnglish
Pages (from-to)90-98
Number of pages9
JournalPharmacology
Volume92
Issue number1-2
DOIs
Publication statusPublished - Sep 2013

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Keywords

  • G2/M arrest
  • Growth inhibition
  • Leukemia cells
  • Lymphoma cells
  • MPT0B169
  • Paclitaxel resistance
  • Tubulin inhibitor

ASJC Scopus subject areas

  • Pharmacology

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