Differential effects of monastrol in two human cell lines

I. Leizerman, R. Avunie-Masala, M. Elkabets, A. Fich, L. Gheber

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

The kinesin-related protein HsEg5 plays essential roles in mitotic spindle dynamics. Although inhibition of HsEg5 has been suggested as an aid in cancer treatment, the effects of such inhibition on human cells have not been characterized. Here we studied the effects of monastrol, an allosteric HsEg5 inhibitor, on AGS and HT29 cell lines and compared them to those of taxol. While both cell lines were similarly sensitive to taxol, AGS cells were more sensitive to monastrol. The differences in sensitivity were determined by the degree of inhibitory effect on cell proliferation, reversibility of monastrol-induced G2/M arrest, intracellular phenotypes and induction of apoptosis. In both cell lines, monastrol-induced apoptosis was accompanied by mitochondrial membrane depolarization and poly-ADP-ribose polymerase 1 cleavage. In AGS, but not HT29 cells, monastrol-induced apoptosis involved a prominent cleavage of procaspases 8 and 3. While in AGS cells, monastrol induced the formation of symmetric microtubule asters only, in HT29 cells, asymmetric asters were also formed, which may be related to specific HsEg5 functions in HT29 cells.

Original languageEnglish
Pages (from-to)2060-2070
Number of pages11
JournalCellular and Molecular Life Sciences
Volume61
Issue number16
DOIs
StatePublished - 1 Jan 2004

Keywords

  • Apoptosis
  • HsEg5
  • Microtubule
  • Mitotic spindle
  • Monastrol
  • Taxol

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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