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Review
. 2021 Sep 20;28(3):437-456.
doi: 10.3390/pathophysiology28030028.

Molecular Functions of Hydrogen Sulfide in Cancer

Rodney E Shackelford  1 , Islam Z Mohammad  1 , Andrew T Meram  2 , David Kim  2 , Fawaz Alotaibi  2 , Stavan Patel  2 , Ghali E Ghali  2 , Christopher G Kevil  1
Affiliations
Review

Molecular Functions of Hydrogen Sulfide in Cancer

Rodney E Shackelford et al. Pathophysiology. .

Abstract

Hydrogen sulfide (H2S) is a gasotransmitter that exerts a multitude of functions in both physiologic and pathophysiologic processes. H2S-synthesizing enzymes are increased in a variety of human malignancies, including colon, prostate, breast, renal, urothelial, ovarian, oral squamous cell, and thyroid cancers. In cancer, H2S promotes tumor growth, cellular and mitochondrial bioenergetics, migration, invasion, angiogenesis, tumor blood flow, metastasis, epithelia-mesenchymal transition, DNA repair, protein sulfhydration, and chemotherapy resistance Additionally, in some malignancies, increased H2S-synthesizing enzyme expression correlates with a worse prognosis and a higher tumor stage. Here we review the role of H2S in cancer, with an emphasis on the molecular mechanisms by which H2S promotes cancer development, progression, dedifferentiation, and metastasis.

Keywords: 3-mercaptopyruvate sulfurtransferase; H2S; cancer; cystathionine β-synthase; cystathionine γ-lyase; hydrogen sulfide.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
A summary of the roles of CBS, 3-MST, and H2S in colon cancer growth, progression, metastasis, and chemotherapy resistance [41,42,43,44,45,46,47,48,49].
Figure 2
Figure 2
A summary of the roles of CBS and H2S in ovarian cancer growth, progression, metastasis, mitochondrial, function, and chemotherapy resistance. O2− is the superoxide radical [51].
Figure 3
Figure 3
A summary of the roles of CBS, CSE, and H2S in breast cancer growth, progression, metastasis, chemotherapy resistance, and resistance to macrophage-generated ROS [54,55,56,57,58,59].
Figure 4
Figure 4
A synopsis of some of the cancer-promoting effects of H2S in cancer. Together, these events function together to increase tumor grade and stage, increase metastatic potential, and confer chemotherapy resistance.
See this image and copyright information in PMC

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