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Review
. 2022 May 25;27(11):3389.
doi: 10.3390/molecules27113389.

Hydrogen Sulfide Biology and Its Role in Cancer

Saadullah Khattak  1 , Mohd Ahmar Rauf  2 , Nazeer Hussain Khan  1 , Qian-Qian Zhang  1 , Hao-Jie Chen  1 , Pir Muhammad  3 , Mohammad Azam Ansari  4 , Mohammad N Alomary  5 , Muhammad Jahangir  6 , Chun-Yang Zhang  7   8 , Xin-Ying Ji  1   9 , Dong-Dong Wu  1   10
Affiliations
Review

Hydrogen Sulfide Biology and Its Role in Cancer

Saadullah Khattak et al. Molecules. .

Abstract

Hydrogen sulfide (H2S) is an endogenous biologically active gas produced in mammalian tissues. It plays a very critical role in many pathophysiological processes in the body. It can be endogenously produced through many enzymes analogous to the cysteine family, while the exogenous source may involve inorganic sulfide salts. H2S has recently been well investigated with regard to the onset of various carcinogenic diseases such as lung, breast, ovaries, colon cancer, and neurodegenerative disorders. H2S is considered an oncogenic gas, and a potential therapeutic target for treating and diagnosing cancers, due to its role in mediating the development of tumorigenesis. Here in this review, an in-detail up-to-date explanation of the potential role of H2S in different malignancies has been reported. The study summarizes the synthesis of H2S, its roles, signaling routes, expressions, and H2S release in various malignancies. Considering the critical importance of this active biological molecule, we believe this review in this esteemed journal will highlight the oncogenic role of H2S in the scientific community.

Keywords: cancer; endogenous gases; hydrogen sulfide; signaling pathways; translational medicine.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
A schematic illustration of the biosynthesis of endogenous H2S in mammals. H2S, hydrogen sulfide; H2O, water; CBS, cystathionine β-synthase; CSE, cystathionine γ-lyase; NH3, ammonia; α-ketoglutarate; 3-MST, 3-mercaptopyruvate sulfurtransferase; CAT, cysteine aminotransferase; 3-MP, 3-mercaptopyruvate; DAO, D-amino acid oxidase.
Figure 2
Figure 2
Dual role of H2S in cancer.
Figure 3
Figure 3
Schematic diagram of pathways of H2S and H2S donors and their derivatives on cancer. H2S and H2S donors participate in regulating several pathways to induce apoptosis and proliferation.
Figure 4
Figure 4
Proposed H2S-induced cytotoxicity pathways in mitochondria. H2S inhibits cytochrome c oxidase, resulting in reduced ATP generation. H2S also impairs calcium homeostasis, resulting in elevated intracellular calcium levels. Reduced glutathione depletion results in reactive oxygen species (ROS). H2S causes DNA damage, protein and lipid persulfidation, and ion channel dysregulation, exacerbated by high intracellular ROS levels. These H2S-induced actions, taken together, may result in programmed cell death. ↑: Increase or Generation; ↓: Decreased or Reduced.
Figure 5
Figure 5
Potential role of H2S in function and mechanisms of action in cancer.
See this image and copyright information in PMC

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