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Hydrogen Sulfide and Cancer.
1Departments of Surgery and Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA, mhellmic@utmb.edu.
Handbook of Experimental Pharmacology
|July 12, 2015
Summary
Hydrogen sulfide (H2S) plays a dual role in cancer. Endogenous H2S promotes tumor growth, while exogenous H2S donors inhibit it, suggesting a bell-shaped dose-response effect for H2S in cancer therapy.
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- Hydrogen sulfide (H2S) and its producing enzymes, like cystathionine-β-synthase (CBS), are increasingly implicated in cancer pathophysiology.
- Elevated H2S levels in colon and ovarian cancers correlate with enhanced tumor growth, spread, and angiogenesis.
Purpose of the Study:
- To review the literature on H2S, H2S donors, and transsulfuration enzymes in various cancers.
- To propose a resolution for the paradoxical roles of H2S in cancer based on its dose-dependent effects.
Main Methods:
- Literature review of studies investigating H2S, H2S donors, and transsulfuration enzymes in cancer.
- Analysis of preclinical data on CBS inhibition and exogenous H2S administration in cancer models.
Main Results:
- Inhibition of CBS or H2S biosynthesis suppressed cancer cell bioenergetics, tumor growth, and metastasis in preclinical models.
- Exogenous H2S donors demonstrated antitumor actions, contradicting findings from H2S biosynthesis inhibition.
Conclusions:
- The paradoxical effects of H2S in cancer can be explained by a bell-shaped dose-response curve: lower endogenous H2S promotes cancer, while higher exogenous H2S inhibits it.
- Targeting CBS and understanding H2S pharmacology are crucial for developing novel anticancer therapies.
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