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Mitotic slippage in non-cancer cells induced by a microtubule disruptor, disorazole C<inf>1</inf>

Xu, FL and Rbaibi, Y and Kiselyov, K and Lazo, JS and Wipf, P and Saunders, WS (2010) Mitotic slippage in non-cancer cells induced by a microtubule disruptor, disorazole C<inf>1</inf>. BMC Chemical Biology, 10.

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Abstract

Background. Disorazoles are polyene macrodiolides isolated from a myxobacterium fermentation broth. Disorazole C was newly synthesized and found to depolymerize microtubules and cause mitotic arrest. Here we examined the cellular responses to disorazole C in both non-cancer and cancer cells and compared our results to vinblastine and taxol. Results. In non-cancer cells, disorazole C induced a prolonged mitotic arrest, followed by mitotic slippage, as confirmed by live cell imaging and cell cycle analysis. This mitotic slippage was associated with cyclin B degradation, but did not require p53. Four assays for apoptosis, including western blotting for poly(ADP-ribose) polymerase cleavage, microscopic analyses for cytochrome C release and annexin V staining, and gel electrophoresis examination for DNA laddering, were conducted and demonstrated little induction of apoptosis in non-cancer cells treated with disorazole C . On the contrary, we observed an activated apoptotic pathway in cancer cells, suggesting that normal and malignant cells respond differently to disorazole C . Conclusion. Our studies demonstrate that non-cancer cells undergo mitotic slippage in a cyclin B-dependent and p53-independent manner after prolonged mitotic arrest caused by disorazole C . In contrast, cancer cells induce the apoptotic pathway after disorazole C treatment, indicating a possibly significant therapeutic window for this compound. © 2010 Xu et al; licensee BioMed Central Ltd. 1 1 1 1 1 1 1


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Xu, FL
Rbaibi, Y
Kiselyov, Kkiselyov@pitt.eduKISELYOV0000-0001-6683-2895
Lazo, JS
Wipf, Ppwipf@pitt.eduPWIPF
Saunders, WSwsaund@pitt.eduWSAUND
Date: 16 March 2010
Date Type: Publication
Journal or Publication Title: BMC Chemical Biology
Volume: 10
DOI or Unique Handle: 10.1186/1472-6769-10-1
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Refereed: Yes
Other ID: NLM PMC2834648
PubMed Central ID: PMC2834648
PubMed ID: 20181182
Date Deposited: 23 Sep 2014 15:28
Last Modified: 27 Mar 2021 09:55
URI: http://d-scholarship.pitt.edu/id/eprint/22232

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