Induction of Apoptosis by Costunolide in Bladder Cancer Cells is Mediated through ROS Generation and Mitochondrial Dysfunction

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.

The NADPH Oxidase Inhibitor Imipramine-Blue in the Treatment of Burkitt Lymphoma

“…Our observations are in line with several publications that described the beneficial effects of ROS inhibition in vitro as well as in clinical trials (15,(35)(36)(37). On the other hand, numerous publications and clinical trials with ROSinducing drugs have shown that an experimental upregulation of ROS may kill cancer cells as well (14,(38)(39)(40). As noted above, ROS levels act in a highly context-dependent manner, and the effects must be determined for each tumor entity.…”

Antiproliferative and apoptotic effects of pinocembrin in human prostate cancer cells

“…These findings revealed that S and G2/ M phase cell cycle arrest was one of the mechanisms through which pinocembrin induces cytotoxicity in LNCaP cells. A number of recent studies have shown that by arresting the cell division at certain checkpoints in the cell cycle, several chemotherapeutic and chemopreventive agents have demonstrated potential antiproliferative effects (Rasul et al, 2013;Rasul et al, 2012b).…”

“…Prevailing treatment options have limited therapeutic success in human prostate cancer, therefore, there is considerable emphasis on identifying novel natural products that selectively induce apoptosis and growth arrest in prostate cancer cells without cytotoxic effects in normal cells (Tsao et al, 2004). In the last few decades, several natural compounds have shown a great promise in treatment of cancer and prevention of metastasis; most of the researchers are interested in and are focusing on finding a cure for cancer and several published reports have identified numerous dietary and botanical natural compounds that have chemopreventive potential (Rasul et al, 2013;Rasul et al, 2012a;Rasul et al, 2012c). Therefore, novel therapeutic agents and treatment approaches are desired to improve the clinical outcome.…”

Dracorhodin perchlorate induces apoptosis in bladder cancer cells through Bcl-2, Bcl-XL, survivin down-regulation and caspase-3 activation

“…More than 50% of neoplasms undergo aberrations in the apoptotic machinery which leads to abnormal cells proliferation (Mashima and (Fulda, 2010;Lawen, 2003;Reed, 2002). Accumulated evidences indicated that most of chemotherapeutic agents halt tumor cells proliferation via induction of apoptosis (Rasul et al, 2013;Rasul et al, 2012a;Rasul et al, 2011a;Rasul et al, 2012b;Rasul et al, 2011d;Rasul et al, 2012b). We examined whether dracorhodin perchlorate inhibited cell growth T24 cells through the induction of apoptosis.…”