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Journal of Biomedicine and Biotechnology
Volume 2009, Article ID 535072, 11 pages
http://dx.doi.org/10.1155/2009/535072
Research Article

YQ36: A Novel Bisindolylmaleimide Analogue Induces KB/VCR Cell Death

Department of Pharmacology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China

Received 25 February 2009; Revised 22 May 2009; Accepted 15 October 2009

Academic Editor: Daniel T. Monaghan

Copyright © 2009 Ji Cao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Overexpression of multidrug resistance proteins P-glycoprotein (P-gp, MDR1) causes resistance of the tumor cells against a variety of chemotherapeutic agents. 3-(1-methyl-1H-indol-3-yl)-1-phenyl-4-(1-(3-(piperidin-1-yl)propyl)-1H-pyrazolo[3,4-b]pyridine-3-yl)-1H-pyrrole-2,5-dione (YQ36) is a novel analogue of bisindolylmaleimide, which has been reported to overcome multidrug resistance. Here, we dedicated to investigate the anticancer activity of YQ36 on KB/VCR cells. The results revealed that YQ36 exhibited great antiproliferative activity on three parental cell lines and MDR1 overexpressed cell lines. Moreover, the hypersensitivity of YQ36 was confirmed on the base of great apoptosis induction and unaltered intracellular drug accumulation in KB/VCR cells. Further results suggested that YQ36 could not be considered as a substrate of P-gp, which contributed to its successfully escaping from the efflux mediated by P-gp. Interestingly, we observed that YQ36 could accumulate in nucleus and induce DNA damage. YQ36 could also induce the activation of caspase-3, imposing effects on the mitochondrial function. Collectively, our data demonstrated that YQ36 exhibited potent activities against MDR cells, inducing DNA damage and triggering subsequent apoptosis via mitochondrial pathway.