Endogenous hydrogen sulfide inhibition suppresses tumor growth by promoting apoptosis and pyroptosis in esophageal cancer cells

Hong Gang Wang, Di Wang, Muhammad Sarfraz, Attia Afzal, Mi Rong Jing, Yan Xia Zhang, Chun Bo Cai, Hui Wen Qi, Hao Jie Chen, Tao Li, Shui Juan Hu, Hong Xia Liu, Xin Ying Ji, Dong Dong Wu

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Background: Hydrogen sulfide (H2S) has been identified as the third gaseous signaling molecule. Endogenous H2S plays a key role in the progression of various types of cancer. However, the effect of endogenous H2S on the growth of esophageal cancer (EC) remains unknown. Methods: In this study, three kinds of H2S-producing enzymes inhibitors, DL-propargylglycine (PAG, inhibitor of cystathionine-γ-lyase), aminooxyacetic acid (AOAA, inhibitor of cystathionine-β-synthase), and L-aspartic acid (L-Asp, inhibitor of 3-mercaptopyruvate sulfurtransferase) were used to determine the role of endogenous H2S in the growth of EC9706 and K450 human EC cells. Results: The results indicated that the combination (PAG+AOAA+L-Asp) group showed higher inhibitory effects on the viability, proliferation, migration, and invasion of EC cells than PAG, AOAA, and L-Asp group. Inhibition of endogenous H2S promoted apoptosis via activation of mitogen-activated protein kinase pathway in EC cells. Endogenous H2S suppression triggered pyroptosis of EC cells by activating reactive oxygen species-mediated nuclear factor-κB signaling pathway. In addition, the combine group showed its more powerful growth-inhibitory effect on the growth of human EC xenograft tumors in nude mice without obvious toxicity. Conclusion: Our results indicate that inhibition of endogenous H2S production can significantly inhibit human EC cell growth via promotion of apoptosis and pyroptosis. Endogenous H2S may be a promising therapeutic target in EC cells. Novel inhibitors for H2S-producing enzymes can be designed and developed for EC treatment.

Original languageEnglish
Article number101770
Pages (from-to)101770
JournalTranslational Oncology
Volume38
DOIs
Publication statusPublished - 01 Dec 2023

Keywords

  • Apoptosis
  • Endogenous HS
  • Esophageal cancer
  • Pyroptosis
  • Signaling pathway

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