Abstract
Increased endogenous hydrogen sulfide (H2S) level by cystathionine β-synthase (CBS) has been shown to closely relate tumorigenesis. H2S promotes angiogenesis, stimulates bioenergy metabolism and inhibits selective phosphatases. However, the role of CBS and H2S in chronic myeloid leukemia (CML) remains elusive. In this study, we found that CBS and H2S 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 H2S levels, promoted mitochondrial-related apoptosis and inhibited the NF-κB-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.
Highlights
We found that CBS expression and endogenous H2S production were increased in the pediatric Chronic myeloid leukemia (CML) patients
The results showed that the CBS mRNA level was significantly increased in CML patients by 2.13 ± 0.34 fold compared with the control groups (P = 0.0033), while the levels of cystathionine γ-synthase (CSE) and 3-MST had no
The tyrosine kinase inhibitors have greatly improved the overall prognosis of CML,[8] there are many concerns, such as the drug tolerance and resistance.[45]
Summary
Chronic myeloid leukemia (CML) is a myeloproliferative malignant clonal disease with abnormal chromosome formation[1,2] that causes the formation of the breakpoint cluster region bcr-abl.[3]. The resulting BCR-ABL fusion protein has abnormal tyrosine kinase activity, leading to the abnormal activation of the downstream molecules and the formation of the malignant clones.[4,5] the tyrosine kinase inhibitors greatly improve CML prognosis,[6,7,8] there are many issues limiting their broader clinical applications, including the fusion protein formation, relapse after drug withdrawal, toxic side effects and the primary and secondary resistance.[9] alternative therapeutic strategies such as new anti-proliferative and/or pro-apoptotic compounds are proposed for treating CML.[10]. Reduction of H2S production by inhibition of CBS expression or activity stimulated leukemia cell apoptosis and inhibited cell proliferation by downregulating NF-κB activity. Our work demonstrates that inhibition of CBS has therapeutic effect on CML
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
