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.
PDF
BIO_PHA_162_2019 - Published Version Restricted to Registered users only Download (4MB) | Request a copy |
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 |
---|---|
Publication: | BIOCHEMICAL PHARMACOLOGY |
Publisher: | PERGAMON-ELSEVIER SCIENCE LTD |
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 |
Date Deposited: | 15 May 2019 10:40 |
Last Modified: | 15 May 2019 10:40 |
URI: | http://eprints.iisc.ac.in/id/eprint/62330 |
Actions (login required)
View Item |