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BubR1 depletion delays apoptosis in the microtubule-depolymerized cells

Naaz, Afsana and Ahad, Shazia and Rai, Ankit and Surolia, Avadhesha and Panda, Dulal (2019) BubR1 depletion delays apoptosis in the microtubule-depolymerized cells. In: BIOCHEMICAL PHARMACOLOGY, 162 (SI). pp. 177-190.

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Official URL: https://doi.org/10.1016/j.bcp.2018.11.015

Abstract

We investigated the role of a spindle assembly checkpoint protein, BubR1, in determining the mechanism of cell killing of an anti-microtubule agent CXI-benzo-84. CXI-benzo-84 dampened microtubule dynamics in live MCF-7 cells. The compound arrested MCF-7 cells in mitosis and induced apoptosis in these cells. Though CXI-benzo-84 efficiently depolymerized microtubules in the BubRl-depleted MCF-7 cells, it did not arrest the BubRl-depleted cells at mitosis. Interestingly, apoptosis occurred in the BubRl-depleted MCF-7 cells in the absence of a mitotic block suggesting that the mitotic block is not a prerequisite for the induction of apoptosis by anti-microtubule agents. In the presence of CXI-Benzo-84, the level of apoptosis was initially found to be lesser in the BubR1-depleted MCF-7 cells than the control cells; however, the BubRl-depleted cells displayed a similar level of apoptosis as the control cells at 72 h of drug treatment. The depletion of BubR1 enhanced DNA damage in MCF-7 cells upon microtubule depolymerization. In addition, CXI-benzo-84 in combination with cisplatin induced more cell death in BubRl-depleted cells than the BubR1-expressing MCF-7 cells. The results indicated a possibility that the BubRl-compromised cancer patients can be treated with combination therapy.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to PERGAMON-ELSEVIER SCIENCE LTD
Keywords: Microtubule-targeting drugs; Microtubule assembly dynamics; BubR1 depletion; Apoptosis; DNA damage
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Depositing User: Id for Latest eprints
Date Deposited: 15 May 2019 10:40
Last Modified: 15 May 2019 10:40
URI: http://eprints.iisc.ac.in/id/eprint/62330

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