Hydrogen sulfide accelerates cell cycle progression in oral squamous cell carcinoma cell lines

OBJECTIVE: To investigate the cell cycle regulator role of the third gaseous transmitter hydrogen sulfide (H2S) in three oral SCC cell lines by using NaHS, a donor of H2S. METHODS: The synchronized oral squamous cell carcinoma cell lines (Cal27, GNM, and WSU-HN6) were treated with different concentrations of NaHS and then subjected to cell proliferation, cell cycle, and Western blot analyses. RESULTS: The CCK-8 assay results showed that the exogenously administered H2S donor, NaHS, induced CAL-27, and GNM cell proliferation in a concentration-dependent manner, and the cell cycle analysis indicated that NaHS accelerated cell cycle progression of the synchronized CAL-27, GNM, and WSU-HN6 cells. Western blot analysis revealed that the cell cycle regulatory genes RPA70 and RB1 were significantly down-regulated and that proliferating cell nuclear antigen (PCNA) and CDK4 were markedly up-regulated by NaHS at specific time points in the cell cycle. In addition, our results indicated that the phosphorylation of Akt and Erk1/2 was involved in exogenous H2S-induced oral SCC cell proliferation. CONCLUSIONS: H2S is a potential pro-proliferative factor of human oral SCC cells that accelerates the progression of the SCC cell cycle; thus, H2S plays a deleterious role in oral SCC cancer development.