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.
Highlights
Urinary bladder cancer is one of the most common urological malignancies worldwide
To identify a novel and specific inducer of Reactive Oxygen Species (ROS) mediated apoptosis in bladder cancer cells, natural compounds were screened in the presence or absence of NAC, a specific ROS scavenger, using the MTT assay
The treatment with costunolide for 24 h inhibited the proliferation of T24 cells in a dose-dependent manner
Summary
Urinary bladder cancer is one of the most common urological malignancies worldwide. More than 12 million new cases of cancer occur annually worldwide. We carried out high throughput screening of compound library from Chinese herbs, using the bladder cancer cell line T24, in the presence or absence of NAC, a specific ROS inhibitor. This screening strategy helped us to identify natural anticancer compounds targeting ROS mediated apoptosis in bladder cancer cells. The objectives of present study were two-fold; to explore the effects of costunolide on the proliferation of T24 cells and to determine the role ROS in costunolide-induced apoptosis in bladder cancer cells with a therapeutic potential. Results showed that costunolide effectively inhibited the proliferation of T24 cells through inducing the apoptosis, which is mediated through ROS generation, mitochondrial dysfunction and activation of caspase-3 and its downstream target Poly (ADP-ribose) polymerase (PARP)
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