Overexpression of CBS/H 2 S inhibits proliferation and metastasis of colon cancer cells through downregulation of CD44

• Published in: Cancer cell international Vol. 22; no. 1; p. 85
• Main Authors: Zhang, Yuyang, Chen, Shanwen, Zhu, Jing, Guo, Shihao, Yue, Taohua, Xu, Hao, Hu, Jianwen, Huang, Zhihao, Chen, Zeyang, Wang, Pengyuan, Liu, Yucun
• Format: Journal Article
• Language: English
• Published: England 16.02.2022
• Subjects: GYY4137; Colorectal cancer; Hydrogen sulfide (H2S); CD44; Cystathionine-beta-synthase (CBS)
• ISSN: 1475-2867; 1475-2867

The role of hydrogen sulfide (H S) in cancer biology is controversial, including colorectal cancer. The bell-shaped effect of H 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 S exerts an inhibitory effect on colon cancer cell proliferation and metastasis. 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 S was detected by H 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. Overexpression of CBS and exogenous H 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 S axis on colon cancer cells. Overexpression of CBS and exogenous provision of H 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.