MPT0B169, a new tubulin inhibitor, inhibits cell growth and induces G2/M arrest in nonresistant and paclitaxel-resistant cancer cells.
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.
Department of Pathology, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan.
Wei-Hwa
WH
Lee
Hsinjin Eugene
HE
Liu
Jang-Yang
JY
Chang
Jing-Ping
JP
Liou
Huei-Mei
HM
Huang
D000972:Antineoplastic Agents, Phytogenic; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D017239:Paclitaxel; D012521:Sarcosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology*
C587776:2-dimethylamino-N-(1-(4-methoxybenzenesulfonyl)-2,3-dihydro-1H-indol-7-yl)acetamide; D000972:Antineoplastic Agents, Phytogenic; D013449:Sulfonamides; D014404:Tubulin; D050257:Tubulin Modulators; D017239:Paclitaxel; D012521:Sarcosine