The Hidden Role of Hydrogen Sulfide Metabolism in Cancer

Abstract

Hydrogen Sulfide (H2S), an endogenously produced gasotransmitter, is involved in various important physiological and disease conditions, including vasodilation, stimulation of cellular bioenergetics, anti-inflammation, and pro-angiogenesis. In cancer, aberrant up-regulation of H2S-producing enzymes is frequently observed in different cancer types. The recognition that tumor-derived H2S plays various roles during cancer development reveals opportunities to target H2S-mediated signaling pathways in cancer therapy. In this review, we will focus on the mechanism of H2S-mediated protein persulfidation and the detailed information about the dysregulation of H2S-producing enzymes and metabolism in different cancer types. We will also provide an update on mechanisms of H2S-mediated cancer progression and summarize current options to modulate H2S production for cancer therapy.

Emerging roles of cystathionine β-synthase in various forms of cancer

“…The data supporting this concept – as well as the challenges related to this approach – e.g. the selective targeting of H 2 S donors to the tumors in vivo , as opposed to the surrounding normal tissues – are discussed in separate review articles [ 140 , 141 , [426] , [427] , [428] , [429] , [430] , [431] ] and will not be covered, in detail, in the current review.…”

Targeted contrast agents and activatable probes for photoacoustic imaging of cancer

“…Hydrogen sulfide (H 2 S) is an endogenous gasotransmitter that plays a role in cellular processes like vasodilation, anti-inflammation, and pro-angiogenesis. 293,294 Due to the overexpression of the H 2 S-producing enzymes (CSE, CBS and 3MST) in many types of cancers, the H 2 S levels in the tumor cells is usually elevated and therefore it is recognized as a biomarker for cancer diagnosis and targeted therapy. However, like many other cancer biomarkers, the role of H 2 S in cancer progression is not fully studied 295,296 and developing chemical tools to visualize H 2 S concentrations in vivo would be important toward this end.…”

Gasotransmitters in the tumor microenvironment: Impacts on cancer chemotherapy (Review)

“…Numerous mechanisms contribute to the pro-tumor effect of H 2 S, including the induction of angiogenesis, regulation of mitochondrial bioenergetics, acceleration of cell cycle progression and anti-apoptotic functions ( 107 ). Furthermore, hypoxia is a common feature of the TME in a number of solid tumors, which affects the level of H 2 S by preventing H 2 S catabolism and consequently stimulating cystathionine γ-lyase gene expression ( 107 ).…”

“…Numerous mechanisms contribute to the pro-tumor effect of H 2 S, including the induction of angiogenesis, regulation of mitochondrial bioenergetics, acceleration of cell cycle progression and anti-apoptotic functions ( 107 ). Furthermore, hypoxia is a common feature of the TME in a number of solid tumors, which affects the level of H 2 S by preventing H 2 S catabolism and consequently stimulating cystathionine γ-lyase gene expression ( 107 ). Furthermore, under the influence of hypoxia in the microenvironment, the levels of H 2 S-producing enzymes are upregulated, and the H 2 S-producing enzymes are transferred toward the mitochondria, which results in increased H 2 S production ( 106 ).…”

“…Previous studies have demonstrated that continuous exposure of cancer cells to a low concentration of H 2 S results in inhibition of cancer progression. This anticancer effect is mainly due to an increase in metabolic lactic acid production by H 2 S and diminishes the pH regulatory system, which consequently leads to intense intracellular acidification and eventually drives cancer cell death ( 107 , 118 ).…”