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  2. Indibulin dampens microtubule dynamics and produces synergistic antiproliferative effect with vinblastine in MCF-7 cells: Implications in cancer chemotherapy

Indibulin dampens microtubule dynamics and produces synergistic antiproliferative effect with vinblastine in MCF-7 cells: Implications in cancer chemotherapy

  • Sci Rep. 2018 Aug 17;8(1):12363. doi: 10.1038/s41598-018-30376-y.
Sonia Kapoor 1 2 Shalini Srivastava 1 Dulal Panda 3
Affiliations

Affiliations

  • 1 Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, 400076, India.
  • 2 Amity Institute of Molecular Medicine and Stem Cell Research, Amity University, Noida, 201313, India.
  • 3 Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, 400076, India. [email protected].
Abstract

Indibulin, a synthetic inhibitor of tubulin assembly, has shown promising Anticancer activity with a minimal neurotoxicity in preclinical animal studies and in Phase I clinical trials for Cancer chemotherapy. Using time-lapse confocal microscopy, we show that 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. The data indicated a possibility that indibulin may reduce chemotherapy-induced peripheral neuropathy in Cancer patients.

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