Indibulin

Indibulin is a synthetic small molecule with antimitotic and potential antineoplastic activities.Indibulin an orally applicable inhibitor of tubulin assembly, shows potent anticancer activity with a minimal neurotoxicity. Indibulin reduces inter-kinetochoric tension, produces aberrant spindles, activates mitotic checkpoint proteins Mad2 and BubR1, and induces mitotic arrest and apoptosis.Indibulin, a synthetic inhibitor of tubulin assembly, has shown promising anticancer activity. Using time-lapse confocal microscopy, indibulin dampens the dynamic instability of individual microtubules in live breast cancer cells. Indibulin treatment also perturbed the localization of end-binding proteins at the growing microtubule ends in MCF-7 cells. Indibulin reduced inter-kinetochoric tension, produced aberrant spindles, activated mitotic checkpoint proteins Mad2 and BubR1, and induced mitotic arrest in MCF-7 cells. Indibulin-treated MCF-7 cells underwent apoptosis-mediated cell death. Further, the combination of indibulin with an anticancer drug vinblastine was found to exert synergistic cytotoxic effects on MCF-7 cells. Interestingly, indibulin displayed a stronger effect on the undifferentiated neuroblastoma (SH-SY5Y) cells than the differentiated neuronal cells. Unlike indibulin, vinblastine and colchicine produced similar depolymerizing effects on microtubules in both differentiated and undifferentiated SH-SY5Y cells.(In Vitro):Indibulin (300-2100 nM; 48 hours) inhibits the proliferation of MCF-7 cells with an IC50 of 150 nM.Indibulin (300, 600 nM; 48 hours) blockes the cells in the G2/M phase indicating that indibulin blockes the progression of the cell cycle at mitosis.Indibulin (150-600 nM; 24 hours) induces apoptosis in MCF-7 cells.Indibulin (150-600 nM; 48 hours) with 300 and 600 nM generates cleaved fragments of PARP protein the treatment of MCF-7 cells.