Overexpression of CBS/H2S inhibits proliferation and metastasis of colon cancer cells through downregulation of CD44

Abstract Background The role of hydrogen sulfide (H 2 S) in cancer biology is controversial, including colorectal cancer. The bell-shaped effect of H 2 S refers to pro-cancer action at lower doses and anti-cancer effect at higher concentrations. We hypothesized that overexpression of cystathionine-beta-synthase (CBS)/H 2 S exerts an inhibitory effect on colon cancer cell proliferation and metastasis. Methods Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8), clone-formation and sphere formation assay. Cell migration was evaluated by transwell migration assay. Intracellular H 2 S was detected by H 2 S probe. Chromatin immunoprecipitation (ChIP) analysis was carried out to examine DNA–protein interaction. Cell experiments also included western blotting, flow cytometry, immunohistochemistry (IHC) and immunofluorescence analysis. We further conducted in vivo experiments to confirm our conclusions. Results Overexpression of CBS and exogenous H 2 S inhibited colon cancer cell proliferation and migration in vitro. In addition, overexpression of CBS attenuated tumor growth and liver metastasis in vivo. Furthermore, CD44 and the transcription factor SP-1 was probably involved in the inhibitory effect of CBS/H 2 S axis on colon cancer cells. Conclusions Overexpression of CBS and exogenous provision of H 2 S inhibited colon cancer cell proliferation and migration both in vivo and in vitro. Molecular mechanisms might involve the participation of CD44 and the transcription factor SP-1.