YQ36: A Novel Bisindolylmaleimide Analogue Induces KB/VCR Cell Death
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 a...
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doaj-18b5397ba2664b479b9be32c503c5b202020-11-25T00:12:32ZengHindawi LimitedJournal of Biomedicine and Biotechnology1110-72431110-72512009-01-01200910.1155/2009/535072535072YQ36: A Novel Bisindolylmaleimide Analogue Induces KB/VCR Cell DeathJi Cao0Lei Zhang1Qing Ye2Xinglu Zhou3Jianshu Lou4Difeng Zhu5Yongzhou Hu6Qiaojun He7Bo Yang8Department of Pharmacology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, ChinaDepartment of Pharmacology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, ChinaDepartment of Pharmacology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, ChinaDepartment of Pharmacology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, ChinaDepartment of Pharmacology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, ChinaDepartment of Pharmacology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, ChinaDepartment of Pharmacology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, ChinaDepartment of Pharmacology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, ChinaDepartment of Pharmacology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, ChinaOverexpression 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.http://dx.doi.org/10.1155/2009/535072 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ji Cao Lei Zhang Qing Ye Xinglu Zhou Jianshu Lou Difeng Zhu Yongzhou Hu Qiaojun He Bo Yang |
spellingShingle |
Ji Cao Lei Zhang Qing Ye Xinglu Zhou Jianshu Lou Difeng Zhu Yongzhou Hu Qiaojun He Bo Yang YQ36: A Novel Bisindolylmaleimide Analogue Induces KB/VCR Cell Death Journal of Biomedicine and Biotechnology |
author_facet |
Ji Cao Lei Zhang Qing Ye Xinglu Zhou Jianshu Lou Difeng Zhu Yongzhou Hu Qiaojun He Bo Yang |
author_sort |
Ji Cao |
title |
YQ36: A Novel Bisindolylmaleimide Analogue Induces KB/VCR Cell Death |
title_short |
YQ36: A Novel Bisindolylmaleimide Analogue Induces KB/VCR Cell Death |
title_full |
YQ36: A Novel Bisindolylmaleimide Analogue Induces KB/VCR Cell Death |
title_fullStr |
YQ36: A Novel Bisindolylmaleimide Analogue Induces KB/VCR Cell Death |
title_full_unstemmed |
YQ36: A Novel Bisindolylmaleimide Analogue Induces KB/VCR Cell Death |
title_sort |
yq36: a novel bisindolylmaleimide analogue induces kb/vcr cell death |
publisher |
Hindawi Limited |
series |
Journal of Biomedicine and Biotechnology |
issn |
1110-7243 1110-7251 |
publishDate |
2009-01-01 |
description |
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. |
url |
http://dx.doi.org/10.1155/2009/535072 |
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