Emerging Roles of Hydrogen Sulfide-metabolizing Enzymes in Cancer

Overview

Journal Redox Rep

Specialties Biochemistry
Biology
Endocrinology

Date 2024 Dec 7

PMID 39643979

Authors

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

Soon will be listed here.

Abstract

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 (HS) is the most recently identified gasotransmitter, which is characterized by its biphasic behavior. At low concentrations, HS 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 HS biosynthesis in mammalian cells and tissues. The focus of this review is the regulation of the various pathways involved in HS 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 HS 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 HS in oncogenesis and tumor progression, one must appreciate the intricate interplay between HS-synthesizing and HS-catabolizing enzymes.

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