Hydrogen Sulfide Lowers Proliferation and Induces Protective Autophagy in Colon Epithelial Cells

by Ya C. Wu, Xiao J. Wang, Le Yu, Francis K. L. Chan, Alfred S. L. Cheng, Jun Yu, Joseph J. Y. Sung, William K. K. Wu, Chi H. Cho

Hydrogen sulfide (H₂S) is a gaseous bacterial metabolite that reaches high levels in the large intestine. In the present study, the effect of H₂S on the proliferation of normal and cancerous colon epithelial cells was investigated. An immortalized colon epithelial cell line (YAMC) and a panel of colon cancer cell lines (HT-29, SW1116, HCT116) were exposed to H₂S at concentrations similar to those found in the human colon. H₂S inhibited normal and cancerous colon epithelial cell proliferation as measured by MTT assay. The anti-mitogenic effect of H₂S was accompanied by G₁-phase cell cycle arrest and the induction of the cyclin-dependent kinase inhibitor p21^Cip. Moreover, exposure to H₂S led to features characteristic of autophagy, including increased formation of LC3B⁺ autophagic vacuoles and acidic vesicular organelles as determined by immunofluorescence and acridine orange staining, respectively. Abolition of autophagy by RNA interference targeting Vps34 or Atg7 enhanced the anti-proliferative effect of H₂S. Further mechanistic investigation revealed that H₂S stimulated the phosphorylation of AMP-activated protein kinase (AMPK) and inhibited the phosphorylation of mammalian target of rapamycin (mTOR) and S6 kinase. Inhibition of AMPK significantly reversed H₂S-induced autophagy and inhibition of cell proliferation. Collectively, we demonstrate that H₂S inhibits colon epithelial cell proliferation and induces protective autophagy via the AMPK pathway.

For the full article visit:
Hydrogen Sulfide Lowers Proliferation and Induces Protective Autophagy in Colon Epithelial Cells
Syndicated from:PLoS ONE

Article is licensed under a Creative Commons Attribution License.