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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Tubulin Modulators
Paclitaxel
Tubulin
Growth
G2 Phase Cell Cycle Checkpoints
Neoplasms
Polymerization
CDC2 Protein Kinase
Cyclin B1
Cell Line
U937 Cells
HL-60 Cells
Colchicine
Microtubules
2-dimethylamino-N-(1-(4-methoxybenzenesulfonyl)-2,3-dihydro-1H-indol-7-yl)acetamide
Lymphoma
Leukemia
Binding Sites
Phosphorylation

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "MPT0B169, a new tubulin inhibitor, inhibits cell growth and induces G2/M Arrest in nonresistant and paclitaxel-resistant cancer cells",
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.",
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author = "Lee, {Wei Hwa} and Liu, {Hsinjin Eugene} and Chang, {Jang Yang} and Liou, {Jing Ping} and Huang, {Huei Mei}",
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T1 - MPT0B169, a new tubulin inhibitor, inhibits cell growth and induces G2/M Arrest in nonresistant and paclitaxel-resistant cancer cells

AU - Lee, Wei Hwa

AU - Liu, Hsinjin Eugene

AU - Chang, Jang Yang

AU - Liou, Jing Ping

AU - Huang, Huei Mei

PY - 2013/9

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N2 - 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.

AB - 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.

KW - G2/M arrest

KW - Growth inhibition

KW - Leukemia cells

KW - Lymphoma cells

KW - MPT0B169

KW - Paclitaxel resistance

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