Inhibition of cystathionine β-synthase promotes apoptosis and reduces cell proliferation in chronic myeloid leukemia

Increased endogenous hydrogen sulfide(H_(2)S)level by cystathionine β-synthase(CBS)has been shown to closely relate tumorigenesis.H_(2)S promotes angiogenesis,stimulates bioenergy metabolism and inhibits selective phosphatases.However,the role of CBS and H_(2)S in chronic myeloid leukemia(CML)remains elusive.In this study,we found that CBS and H_(2)S levels were increased in the bone marrow mononuclear cells of pediatric CML patients,as well as in the CML-derived K562 cells and CBS expression levels were correlated with different disease phases.Inhibition of CBS reduced the proliferation of the CML primary bone marrow mononuclear cells and induced growth inhibition,apoptosis,cell cycle arrest,and migration suppression in K562 cells and tumor xenografts.The knockdown of CBS expression by shRNA and inhibiting CBS activity by AOAA decreased the endogenous H_(2)S levels,promoted mitochondrial-related apoptosis and inhibited the NF-xB-mediated gene expression.Our study suggests that inhibition of CBS induces cell apoptosis,as well as limits cell proliferation and migration,a potential target for the treatment of chronic myeloid leukemia.