Abstract
The effects of vitamin K2 on apoptosis in a variety of cancer cells have been well established in previous studies. However, the apoptotic effect of vitamin K2 on bladder cancer cells has not been evaluated. The aim of this study is to examine the apoptotic activity of Vitamin K2 in bladder cancer cells and investigate the underlying mechanism. In this study, Vitamin K2 induced apoptosis in bladder cancer cells through mitochondria pathway including loss of mitochondria membrane potential, cytochrome C release and caspase-3 cascade. Furthermore, the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAPK was detected in Vitamin K2-treated cells and both SP600125 (an inhibitor of JNK) and SB203580 (an inhibitor of p38 MAPK) completely abolished the Vitamin K2-induced apoptosis and loss of mitochondria membrane potential. Moreover, the generation of reactive oxygen species (ROS) was detected in bladder cancer cells, upon treatment of vitamin K2 and the anti-oxidant N-acetyl cysteine (NAC) almost blocked the Vitamin K2-triggered apoptosis, loss of mitochondria membrane potential and activation of JNK and p38 MAPK. Taken together, these findings revealed that Vitamin K2 induces apoptosis in bladder cancer cells via ROS-mediated JNK/p38 MAPK and Mitochondrial pathways.
Highlights
Bladder cancer is one of the most common carcinoma and ranks the ninth in worldwide cancer incidence
The generation of reactive oxygen species (ROS) was detected in bladder cancer cells, upon treatment of vitamin K2 and the anti-oxidant N-acetyl cysteine (NAC) almost blocked the Vitamin K2-triggered apoptosis, loss of mitochondria membrane potential and activation of Jun N-terminal kinase (JNK) and p38 MAPK. These findings revealed that Vitamin K2 induces apoptosis in bladder cancer cells via ROS-mediated JNK/p38 MAPK and Mitochondrial pathways
Viability of human normal cells (L02 and HEK293) was minimally affected after exposed to high concentration (100 μM) of Vitamin K2 (S1A Fig). These results suggest that vitamin K2 has anticancer activity in human bladder cancer cells, with low cytotoxic effect on human normal cells
Summary
Bladder cancer is one of the most common carcinoma and ranks the ninth in worldwide cancer incidence. To cure human bladder cancer, traditional and current methods, such as radical cystectomy, chemotherapy, radiotherapy, concurrent chemotherapy and radotherapy, combination of radical cystectomy and chemotherapy and immunotherapy, are widely used[1,3,4,5]. These therapies usually encounter a variety of adverse effect such as distant metastasis, local recurrence, toxicity to health, low survival of patients and cost-effectiveness. Base on the above side effect and poor life quality of patients[4,6,7], new drugs are urgently required to treat bladder carcinoma
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