Molecular Functions of Hydrogen Sulfide in Cancer

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.

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

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

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

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.