Hydrogen Sulfide Demonstrates Promising Antitumor Efficacy in Gastric Carcinoma by Targeting MGAT5()()

Mannosyl (alpha-1,6-)-Glycoprotein beta-1,6-N-acetyl-glucosaminyltransferase (MGAT5) is exclusively expressed in gastric carcinoma, and plays an essential role in cancer progression, but no targeted drug is available so far. The potential anti-cancer effect of Hydrogen Sulfide (H(2)S), has not been widely recognized. It intrigued broad interest to explore the clinical benefits of cancer therapy, with the current understanding of molecular mechanisms of H(2)S which remains very limited. In this study, we identify that H(2)S is an effective inhibitor of MGAT5, leading to reduce the expression of exclusively abnormal glycoprotein processes in gastric carcinoma. H(2)S specifically dissociation of karyopherin subunit alpha-2 (KPNA2) with Jun proto-oncogene (c-Jun) interaction, and blocking c-Jun nuclear translocation, and downregulation of MGAT5 expression at the level of gene and protein. Consequently, H(2)S impairs growth and metastasis in gastric carcinoma by targeting inhibits MGAT5 activity. In an animal tumor model study, H(2)S is well tolerated, inhibits gastric carcinoma growth and metastasis. Our preclinical work therefore supports that H(2)S acts as a novel inhibitor of MGAT5 that block tumorigenesis in gastric carcinoma. SIGNIFICANCE: This study shows that H(2)S can effective targeting inhibits MGAT5 activity, and demonstrates promising antitumor efficacy. These findings gain mechanistic insights into the anti-cancer capacity of H(2)S and may provide useful information for the clinical explorations of H(2)S in cancer treatment.