Research Article

Cellular and Molecular Life Sciences CMLS

, Volume 61, Issue 16, pp 2060-2070

First online:

Differential effects of monastrol in two human cell lines

  • I. LeizermanAffiliated withDepartment of Clinical Biochemistry, Ben-Gurion University of the Negev
  • , R. Avunie-MasalaAffiliated withDepartment of Clinical Biochemistry, Ben-Gurion University of the Negev
  • , M. ElkabetsAffiliated withDepartment of Clinical Biochemistry, Ben-Gurion University of the Negev
  • , A. FichAffiliated withDepartment of Gastroenterology, Ben-Gurion University of the Negev and Soroka University Medical Center
  • , L. GheberAffiliated withDepartment of Clinical Biochemistry, Ben-Gurion University of the NegevDepartment of Gastroenterology, Ben-Gurion University of the Negev and Soroka University Medical Center Email author 

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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.

Monastrol HsEg5 mitotic spindle microtubule taxol apoptosis