Increased H(2)S and its synthases in urothelial cell carcinoma of the bladder, and enhanced cisplatin-induced apoptosis following H(2)S inhibition in EJ cells

H(2)S, synthesized by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (MPST), functions as a signalling molecule in mammalian cells. H(2)S serves complex functions in physiological and pathological processes, including in bladder cancer. In the present study, H(2)S production, the expression of the associated enzymes and the effect of H(2)S on human urothelial cell carcinoma of the bladder (UCB) tissue and cell lines were evaluated, and whether decreasing H(2)S levels influenced cell viability and tumour growth following treatment with cisplatin (CDDP) was assessed in UCB cells in vitro and in vivo. H(2)S production and the expression of CBS, CSE and MPST in bladder tissue specimens and the UCB cell lines 5637, EJ and UM-UC-3 were analysed using a sulfur-sensitive electrode and western blotting. UCB cells were subjected to different treatments, and viability and protein expression were determined. H(2)S production was inhibited to examine its influence on EJ cell tumour growth following CDDP treatment in vivo. It was identified that CBS, CSE and MPST protein were up-regulated in UCB tissues and cells. The H(2)S production and enzyme expression levels were the highest in UCB tissue and EJ cells. The inhibition of endogenous H(2)S biosynthesis decreased EJ cell viability and tumour growth in response to CDDP treatment. H(2)S levels and the associated biosynthetic enzymes were increased in human UCB tissue and cells compared with adjacent tissue and normal cells, which may have increased the resistance to CDDP-induced apoptosis in UCB. Therefore, H(2)S and its production may be an alternative therapeutic target for UCB.