Molecular Functions of Hydrogen Sulfide in Cancer
Abstract
:1. Introduction
2. H2S Chemistry, Synthesis, and Molecular Mechanisms of Action
2.1. H2S Chemistry
2.2. H2S Synthesis
2.3. Molecular Mechanisms of H2S Activity
3. H2S and Cancer
3.1. H2S and Colorectal Cancer
3.2. H2S and Ovarian Cancer
3.3. Breast Cancer
3.4. Bladder Cancer
3.5. Renal Cancer
3.6. Prostate Cancer
3.7. Thyroid
3.8. Pulmonary Adenocarcinoma
3.9. Melanoma
3.10. Oral Squamous Cell Carcinoma
4. Protein Sulfhydration and Cancer
4.1. NF-κB
4.2. GAPDH
4.3. Lactate Dehydrogenase (LDHA)
5. Polysulfides and Cancer
6. H2S-Associated Tumor Markers in Bodily Gas and Fluids
7. H2S and Nuclear DNA Repair
8. The Immunomodulatory Role of H2S in Cancer
9. Conclusions, Issues, and Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Tumor Type | H2S Synthesizing Enzyme Expression | Comments | References |
---|---|---|---|
Colon Cancer | CBS increased | Higher colon cancer CBS promotes cancer growth, mitochondrial bioenergetic activity, and increased glycolysis, migration, invasion, and chemotherapy resistance. While not increased, 3-MST expression promotes colon cancer EMT. | [42,43,48,49] |
Ovarian Cancer | CBS and CSE increased | Increased CBS and CSE promote events including cancer growth, more active mitochondrial bioenergetics and morphologic integrity, migration, invasion, chemotherapy resistance, and a poor prognosis. Data also indicates a role for polysulfides in ovarian cancer. | [36,51,52] |
Breast Cancer | CBS and CSE increased | Increased CBS and CSE promote cell growth, migration, and chemotherapy resistance. Membranous CBS protects cells from macrophage-derived ROS and confers a worse prognosis. CSE promotes breast cancer metastasis. | [39,56,58] |
Bladder Cancer | CBS, CSE, and 3-MST increased | H2S likely promotes bladder cancer cell proliferation and invasion, and MMP-2 and MMP-9 protein expression. H2S synthesis in tumor lysates positively correlates with tumor stage and grade. | [61,62] |
Renal Cancer | Most studies show suppressed or unchanged expression | H2S appears to promote tumor growth. The present studies show contradictory results, possibly based on analysis methods employed. | [64,65,66] |
Prostate Cancer | Increased or decreased CSE in different studies | CSE promotes cell proliferation, migration, invasion, and poor patient survival. CSE promotes cell migration by an enzymatic activity-independent mechanism. Another study shows that CSE suppression promotes prostatic cancer. | [68,69] |
Thyroid Cancer | CBS and CSE increased | Different studies show increased CBS or CSE. NaHS promotes thyroid cancer proliferation, migration, and cell viability. | [71,72,73] |
Pulmonary adenocarcinoma | CBS, CSE, and 3-MST increased | H2S promotes cell proliferation, mitochondrial bioenergetics, and mitochondrial DNA repair. | [74] |
Melanoma | Mildly increased CSE expression | CSE expression inhibited melanoma cell growth and H2S donors increased apoptosis by NF-κB inhibition. | [76] |
Oral squamous cell carcinoma | CBS, CSE, and 3-MST increased | Direct measurements of tumor H2S concentrations revealed 13% higher H2S than in adjacent benign oral squamous epithelium. | [16] |
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Shackelford, R.E.; Mohammad, I.Z.; Meram, A.T.; Kim, D.; Alotaibi, F.; Patel, S.; Ghali, G.E.; Kevil, C.G. Molecular Functions of Hydrogen Sulfide in Cancer. Pathophysiology 2021, 28, 437-456. https://doi.org/10.3390/pathophysiology28030028
Shackelford RE, Mohammad IZ, Meram AT, Kim D, Alotaibi F, Patel S, Ghali GE, Kevil CG. Molecular Functions of Hydrogen Sulfide in Cancer. Pathophysiology. 2021; 28(3):437-456. https://doi.org/10.3390/pathophysiology28030028
Chicago/Turabian StyleShackelford, Rodney E., Islam Z. Mohammad, Andrew T. Meram, David Kim, Fawaz Alotaibi, Stavan Patel, Ghali E. Ghali, and Christopher G. Kevil. 2021. "Molecular Functions of Hydrogen Sulfide in Cancer" Pathophysiology 28, no. 3: 437-456. https://doi.org/10.3390/pathophysiology28030028