Inhibition of endogenous hydrogen sulfide production suppresses the growth of nasopharyngeal carcinoma cells

Abstract

AbstractHydrogen sulfide (H2S) has been widely recognized as one of gasotransmitters. Endogenous H2S plays a crucial role in the progression of cancer. However, the effect of endogenous H2S on the development of nasopharyngeal carcinoma (NPC) is still unknown. In this study, aminooxyacetic acid (AOAA, an inhibitor of cystathionine‐β‐synthase), dl‐propargylglycine (PAG, an inhibitor of cystathionine‐γ‐lyase), and l‐aspartic acid (l‐Asp, an inhibitor of 3‐mercaptopyruvate sulfurtransferase) were adopted to detect the role of endogenous H2S in NPC growth. The results indicated that the combine (PAG + AOAA + l‐Asp) group had higher inhibitory effect on the growth of NPC cells than the PAG, AOAA, and l‐Asp groups. There were similar trends in the levels of apoptosis and reactive oxygen species (ROS). In addition, the combine group exhibited lower levels of phospho (p)‐extracellular signal‐regulated protein kinase but higher expressions of p‐p38 and p‐c‐Jun N‐terminal kinase than those in the AOAA, PAG, and l‐Asp groups. Furthermore, the combine group exerted more potent inhibitory effect on NPC xenograft tumor growth without obvious toxicity. In summary, suppression of endogenous H2S generation could dramatically inhibit NPC growth via the ROS/mitogen‐activated protein kinase pathway. Endogenous H2S may be a novel therapeutic target in human NPC cells. Effective inhibitors for H2S‐producing enzymes could be designed and developed for NPC treatment.