Emerging roles of hydrogen sulfide-metabolizing enzymes in cancer
Alyaa Dawoud,
Rana A. Youness,
Kareem Elsayed,
Heba Nafae,
Hoda Allam,
Hager Adel Saad,
Carole Bourquin,
Csaba Szabo,
Reham Abdel-Kader,
Mohamed Z. Gad
Affiliations
Alyaa Dawoud
Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), New Cairo, Egypt
Rana A. Youness
Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), New Cairo, Egypt
Kareem Elsayed
Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), New Cairo, Egypt
Heba Nafae
Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), New Cairo, Egypt
Hoda Allam
Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), New Cairo, Egypt
Hager Adel Saad
Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), New Cairo, Egypt
Carole Bourquin
School of Pharmaceutical Sciences, Institute of Pharmaceutical Sciences of Western Switzerland, Department of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine, University of Geneva, Geneva, Switzerland
Csaba Szabo
Chair of Pharmacology, Section of Science and Medicine, University of Fribourg, Fribourg, Switzerland
Reham Abdel-Kader
Pharmacology and Toxicology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), New Cairo, Egypt
Mohamed Z. Gad
Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), New Cairo, Egypt
Gasotransmitters play crucial roles in regulating many physiological processes, including cell signaling, cellular proliferation, angiogenesis, mitochondrial function, antioxidant production, nervous system functions and immune responses. Hydrogen sulfide (H2S) is the most recently identified gasotransmitter, which is characterized by its biphasic behavior. At low concentrations, H2S promotes cellular bioenergetics, whereas at high concentrations, it can exert cytotoxic effects. Cystathionine β-synthetase (CBS), cystathionine-γ-lyase (CSE), 3-mercaptopyruvate sulfurtransferase (3-MST), and cysteinyl-tRNA synthetase 2 (CARS2) are pivotal players in H2S biosynthesis in mammalian cells and tissues. The focus of this review is the regulation of the various pathways involved in H2S metabolism in various forms of cancer. Key enzymes in this process include the sulfide oxidation unit (SOU), which includes sulfide:quinone oxidoreductase (SQOR), human ethylmalonic encephalopathy protein 1 (hETHE1), rhodanese, sulfite oxidase (SUOX/SO), and cytochrome c oxidase (CcO) enzymes. Furthermore, the potential role of H2S methylation processes mediated by thiol S-methyltransferase (TMT) and thioether S-methyltransferase (TEMT) is outlined in cancer biology, with potential opportunities for targeting them for clinical translation. In order to understand the role of H2S in oncogenesis and tumor progression, one must appreciate the intricate interplay between H2S-synthesizing and H2S-catabolizing enzymes.
