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Induction of Apoptosis by Costunolide in Bladder Cancer Cells is Mediated through ROS Generation and Mitochondrial Dysfunction
Dental Hospital, Jilin University, Changchun 130041, China
The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China
Department of Public Health, Tohoku University, Sendai 9808576, Japan
* Authors to whom correspondence should be addressed.
Received: 26 November 2012; in revised form: 15 January 2013 / Accepted: 16 January 2013 / Published: 24 January 2013
Abstract: Despite the availability of several therapeutic options, a safer and more effective modality is urgently needed for treatment of bladder cancer. Costunolide, a member of sesquiterpene lactone family, possesses potent anticancer properties. In this study, for the first time we investigated the effects of costunolide on the cell viability and apoptosis in human bladder cancer T24 cells. Treatment of T24 cells with costunolide resulted in a dose-dependent inhibition of cell viability and induction of apoptosis which was associated with the generation of ROS and disruption of mitochondrial membrane potential (Δψm). These effects were significantly blocked when the cells were pretreated with N-acetyl- cysteine (NAC), a specific ROS inhibitor. Exposure of T24 cells to costunolide was also associated with increased expression of Bax, down-regulation of Bcl-2, survivin and significant activation of caspase-3, and its downstream target PARP. These findings provide the rationale for further in vivo and clinical investigation of costunolide against human bladder cancer.
Keywords: bladder cancer; T24 cells; costunolide; apoptosis; reactive oxygen species
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MDPI and ACS Style
Rasul, A.; Bao, R.; Malhi, M.; Zhao, B.; Tsuji, I.; Li, J.; Li, X. Induction of Apoptosis by Costunolide in Bladder Cancer Cells is Mediated through ROS Generation and Mitochondrial Dysfunction. Molecules 2013, 18, 1418-1433.
Rasul A, Bao R, Malhi M, Zhao B, Tsuji I, Li J, Li X. Induction of Apoptosis by Costunolide in Bladder Cancer Cells is Mediated through ROS Generation and Mitochondrial Dysfunction. Molecules. 2013; 18(2):1418-1433.
Rasul, Azhar; Bao, Rui; Malhi, Mahadev; Zhao, Bing; Tsuji, Ichiro; Li, Jiang; Li, Xiaomeng. 2013. "Induction of Apoptosis by Costunolide in Bladder Cancer Cells is Mediated through ROS Generation and Mitochondrial Dysfunction." Molecules 18, no. 2: 1418-1433.