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


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.

SUBMITTER: Wang HG 

PROVIDER: S-EPMC10514559 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

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

Wang Hong-Gang HG   Wang Di D   Sarfraz Muhammad M   Afzal Attia A   Jing Mi-Rong MR   Zhang Yan-Xia YX   Cai Chun-Bo CB   Qi Hui-Wen HW   Chen Hao-Jie HJ   Li Tao T   Hu Shui-Juan SJ   Liu Hong-Xia HX   Ji Xin-Ying XY   Wu Dong-Dong DD  

Translational oncology 20230915


<h4>Background</h4>Hydrogen sulfide (H<sub>2</sub>S) has been identified as the third gaseous signaling molecule. Endogenous H<sub>2</sub>S plays a key role in the progression of various types of cancer. However, the effect of endogenous H<sub>2</sub>S on the growth of esophageal cancer (EC) remains unknown.<h4>Methods</h4>In this study, three kinds of H<sub>2</sub>S-producing enzymes inhibitors, DL-propargylglycine (PAG, inhibitor of cystathionine-γ-lyase), aminooxyacetic acid (AOAA, inhibitor  ...[more]

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