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Molecules 2012, 17(5), 5442-5458; doi:10.3390/molecules17055442
Article

FG020326 Sensitized Multidrug Resistant Cancer Cells to Docetaxel-Mediated Apoptosis via Enhancement of Caspases Activation

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Received: 13 March 2012; in revised form: 21 April 2012 / Accepted: 28 April 2012 / Published: 9 May 2012
(This article belongs to the Section Medicinal Chemistry)
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Abstract: Apoptotic resistance is the main obstacle for treating cancer patients with chemotherapeutic drugs. Multidrug resistance (MDR) is often characterized by the expression of P-glycoprotein (P-gp), a 170-KD ATP-dependent drug efflux protein. Functional P-gp can confer resistance to activate caspase-8 and -3 dependent apoptosis induced by a range of different stimuli, including tumor necrosis and chemotherapeutic drugs such as docetaxel and vincristine. We demonstrated here that comparison of sensitive KB cells, P-gp positive (P-gp+ve) KBv200 cells were extremely resistant to apoptosis induced by docetaxel. FG020326, a pharmacological inhibitor of P-gp function, could enhance concentration-dependently the effect of docetaxel on cell apoptosis and sensitize caspase-8, -9 and -3 activation in P-gp overexpressing KBv200 cells, but not in KB cells. Therefore, the enhancement of caspase-8, -9 and -3 activation induced by docetaxel may be one of the key mechanisms of the reversal of P-gp mediated docetaxel resistance by FG020326.
Keywords: cancer; multiple drug resistance; FG020326; P-glycoprotein; apoptosis; caspase cancer; multiple drug resistance; FG020326; P-glycoprotein; apoptosis; caspase
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.

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MDPI and ACS Style

Wang, X.-W.; Wang, X.-K.; Zhang, X.; Liang, Y.-J.; Shi, Z.; Chen, L.-M.; Fu, L.-W. FG020326 Sensitized Multidrug Resistant Cancer Cells to Docetaxel-Mediated Apoptosis via Enhancement of Caspases Activation. Molecules 2012, 17, 5442-5458.

AMA Style

Wang X-W, Wang X-K, Zhang X, Liang Y-J, Shi Z, Chen L-M, Fu L-W. FG020326 Sensitized Multidrug Resistant Cancer Cells to Docetaxel-Mediated Apoptosis via Enhancement of Caspases Activation. Molecules. 2012; 17(5):5442-5458.

Chicago/Turabian Style

Wang, Xiu-Wen; Wang, Xiao-Kun; Zhang, Xu; Liang, Yong-Ju; Shi, Zhi; Chen, Li-Ming; Fu, Li-Wu. 2012. "FG020326 Sensitized Multidrug Resistant Cancer Cells to Docetaxel-Mediated Apoptosis via Enhancement of Caspases Activation." Molecules 17, no. 5: 5442-5458.



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