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Please use this identifier to cite or link to this item: http://dspace.library.iitb.ac.in/jspui/handle/10054/5176

Title: Suppression of microtubule dynamics by benomyl decreases tension across kinetochore pairs and induces apoptosis in cancer cells
Authors: RATHINASAMY, K
PANDA, D
Keywords: directional instability
chromosome congression
spindle checkpoint
anticancer drugs
mitotic spindle
protein-kinase
anaphase onset
attachment
binding
bcl-2
Issue Date: 2006
Publisher: BLACKWELL PUBLISHING
Citation: FEBS JOURNAL, 273(17), 4114-4128
Abstract: We found that benomyl, a benzimidazole fungicide, strongly suppressed the reassembly of cold-depolymerized spindle microtubules in HeLa cells. Benomyl perturbed microtubule-kinetochore attachment and chromosome alignment at the metaphase plate. Benomyl also significantly decreased the distance between the sister kinetochore pairs in metaphase cells and increased the level of the checkpoint protein BubR1 at the kinetochore region, indicating that benomyl caused loss of tension across the kinetochores. In addition, benomyl decreased the intercentrosomal distance in mitotic HeLa cells and blocked the cells at mitosis. Further, we analyzed the effects of benomyl on the signal transduction pathways in relation to mitotic block, bcl2 phosphorylation and induction of apoptosis. The results suggest that benomyl causes loss of tension across the kinetochores, blocks the cell cycle progression at mitosis and subsequently, induces apoptosis through the bcl2-bax pathway in a manner qualitatively similar to the powerful microtubule targeted anticancer drugs like the vinca alkaloids and paclitaxel. Considering the very high toxicity of the potent anticancer drugs and the low toxicity of benomyl in humans, we suggest that benomyl could be useful as an adjuvant in combination with the powerful anticancer drugs in cancer therapy.
URI: http://dx.doi.org/10.1111/j.1742-4658.2006.05413.x
http://dspace.library.iitb.ac.in/xmlui/handle/10054/5176
http://hdl.handle.net/10054/5176
ISSN: 1742-464X
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