Inhibition of the microtubule-based mitotic spindle function and subsequent inhibition of mitosis has been a target of numerous anticancer drugs. However, until recently, such drugs inhibited microtubule dynamics thus also causing side effects in non-dividing cells. Recently, a cell-permeable molecule (monastrol) was discovered that inhibits mitotic spindle function without targeting microtubules. Monastrol inhibits the activity of the mitotic kinesin-5 motor protein (Eg5), which is essential for spindle formation.

     We have previously reported that upon monastrol treatment, HT29 and AGS cells arrest in mitosis and undergo apoptosis, with AGS being considerably more sensitive compared to HT29 cells. http://www.ncbi.nlm.nih.gov/pubmed/15316655.

     We currently are studying the mechanisms that underlie the differential sensitivity of human cell-lines to monastrol.

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Effect of monastrol on AGS cells from human gastric carcinoma
 

prolonged effect of monastrol on AGS and HT29 cells.