Potential role of the 3-mercaptopyruvate sulfurtransferase (3-MST)—hydrogen sulfide (H2S) pathway in cancer cells

Fiona Augsburger, Csaba Szabo

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Hydrogen sulfide (H2S), produced by various endogenous enzyme systems, serves various biological regulatory roles in mammalian cells in health and disease. Over recent years, a new concept emerged in the field of H2S biology, showing that various cancer cells upregulate their endogenous H2S production, and utilize this mediator in autocrine and paracrine manner to stimulate proliferation, bioenergetics and tumor angiogenesis. Initial work identified cystathionine-beta-synthase (CBS) in many tumor cells as the key source of H2S. In other cells, cystathionine-gamma-lyase (CSE) has been shown to play a pathogenetic role. However, until recently, less attention has been paid to the third enzymatic source of H2S, 3-mercaptopyruvate sulfurtransferase (3-MST), even though several of its biological and biochemical features - e.g. its partial mitochondrial localization, its ability to produce polysulfides, which, in turn, can induce functionally relevant posttranslational protein modifications - makes it a potential candidate. Indeed, several lines of recent data indicate the potential role of the 3-MST system in cancer biology. In many cancers (e.g. colon adenocarcinoma, lung adenocarcinoma, urothelial cell carcinoma, various forms of oral carcinomas), 3-MST is upregulated compared to the surrounding normal tissue. According to in vitro studies, 3-MST upregulation is especially prominent in cancer cells that recover from oxidative damage and/or develop a multidrug-resistant phenotype. Emerging data with newly discovered pharmacological inhibitors of 3-MST, as well as data using 3-MST silencing approaches suggest that the 3-MST/H2S system plays a role in maintaining cancer cell proliferation; it may also regulate bioenergetic and cell-signaling functions. Many questions remain open in the field of 3-MST/cancer biology; the last section of current article highlights these open questions and lays out potential experimental strategies to address them.

Original languageEnglish (US)
JournalPharmacological Research
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

Fingerprint

Hydrogen Sulfide
Neoplasms
Energy Metabolism
Up-Regulation
Cystathionine gamma-Lyase
Cystathionine beta-Synthase
Carcinoma
3-mercaptopyruvic acid
Post Translational Protein Processing
Colonic Neoplasms
Cell Proliferation
Pharmacology
Phenotype
Health
Enzymes

Keywords

  • 3-mercaptopyruvate sulfurtransferase
  • Angiogenesis
  • Cell death
  • Cell proliferation
  • Cystathionine-β-synthases
  • Cystathionine-γ-lyase
  • Gasotransmitters
  • Nitric oxide

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Potential role of the 3-mercaptopyruvate sulfurtransferase (3-MST)—hydrogen sulfide (H2S) pathway in cancer cells",
abstract = "Hydrogen sulfide (H2S), produced by various endogenous enzyme systems, serves various biological regulatory roles in mammalian cells in health and disease. Over recent years, a new concept emerged in the field of H2S biology, showing that various cancer cells upregulate their endogenous H2S production, and utilize this mediator in autocrine and paracrine manner to stimulate proliferation, bioenergetics and tumor angiogenesis. Initial work identified cystathionine-beta-synthase (CBS) in many tumor cells as the key source of H2S. In other cells, cystathionine-gamma-lyase (CSE) has been shown to play a pathogenetic role. However, until recently, less attention has been paid to the third enzymatic source of H2S, 3-mercaptopyruvate sulfurtransferase (3-MST), even though several of its biological and biochemical features - e.g. its partial mitochondrial localization, its ability to produce polysulfides, which, in turn, can induce functionally relevant posttranslational protein modifications - makes it a potential candidate. Indeed, several lines of recent data indicate the potential role of the 3-MST system in cancer biology. In many cancers (e.g. colon adenocarcinoma, lung adenocarcinoma, urothelial cell carcinoma, various forms of oral carcinomas), 3-MST is upregulated compared to the surrounding normal tissue. According to in vitro studies, 3-MST upregulation is especially prominent in cancer cells that recover from oxidative damage and/or develop a multidrug-resistant phenotype. Emerging data with newly discovered pharmacological inhibitors of 3-MST, as well as data using 3-MST silencing approaches suggest that the 3-MST/H2S system plays a role in maintaining cancer cell proliferation; it may also regulate bioenergetic and cell-signaling functions. Many questions remain open in the field of 3-MST/cancer biology; the last section of current article highlights these open questions and lays out potential experimental strategies to address them.",
keywords = "3-mercaptopyruvate sulfurtransferase, Angiogenesis, Cell death, Cell proliferation, Cystathionine-β-synthases, Cystathionine-γ-lyase, Gasotransmitters, Nitric oxide",
author = "Fiona Augsburger and Csaba Szabo",
year = "2018",
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doi = "10.1016/j.phrs.2018.11.034",
language = "English (US)",
journal = "Pharmacological Research",
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T1 - Potential role of the 3-mercaptopyruvate sulfurtransferase (3-MST)—hydrogen sulfide (H2S) pathway in cancer cells

AU - Augsburger, Fiona

AU - Szabo, Csaba

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Hydrogen sulfide (H2S), produced by various endogenous enzyme systems, serves various biological regulatory roles in mammalian cells in health and disease. Over recent years, a new concept emerged in the field of H2S biology, showing that various cancer cells upregulate their endogenous H2S production, and utilize this mediator in autocrine and paracrine manner to stimulate proliferation, bioenergetics and tumor angiogenesis. Initial work identified cystathionine-beta-synthase (CBS) in many tumor cells as the key source of H2S. In other cells, cystathionine-gamma-lyase (CSE) has been shown to play a pathogenetic role. However, until recently, less attention has been paid to the third enzymatic source of H2S, 3-mercaptopyruvate sulfurtransferase (3-MST), even though several of its biological and biochemical features - e.g. its partial mitochondrial localization, its ability to produce polysulfides, which, in turn, can induce functionally relevant posttranslational protein modifications - makes it a potential candidate. Indeed, several lines of recent data indicate the potential role of the 3-MST system in cancer biology. In many cancers (e.g. colon adenocarcinoma, lung adenocarcinoma, urothelial cell carcinoma, various forms of oral carcinomas), 3-MST is upregulated compared to the surrounding normal tissue. According to in vitro studies, 3-MST upregulation is especially prominent in cancer cells that recover from oxidative damage and/or develop a multidrug-resistant phenotype. Emerging data with newly discovered pharmacological inhibitors of 3-MST, as well as data using 3-MST silencing approaches suggest that the 3-MST/H2S system plays a role in maintaining cancer cell proliferation; it may also regulate bioenergetic and cell-signaling functions. Many questions remain open in the field of 3-MST/cancer biology; the last section of current article highlights these open questions and lays out potential experimental strategies to address them.

AB - Hydrogen sulfide (H2S), produced by various endogenous enzyme systems, serves various biological regulatory roles in mammalian cells in health and disease. Over recent years, a new concept emerged in the field of H2S biology, showing that various cancer cells upregulate their endogenous H2S production, and utilize this mediator in autocrine and paracrine manner to stimulate proliferation, bioenergetics and tumor angiogenesis. Initial work identified cystathionine-beta-synthase (CBS) in many tumor cells as the key source of H2S. In other cells, cystathionine-gamma-lyase (CSE) has been shown to play a pathogenetic role. However, until recently, less attention has been paid to the third enzymatic source of H2S, 3-mercaptopyruvate sulfurtransferase (3-MST), even though several of its biological and biochemical features - e.g. its partial mitochondrial localization, its ability to produce polysulfides, which, in turn, can induce functionally relevant posttranslational protein modifications - makes it a potential candidate. Indeed, several lines of recent data indicate the potential role of the 3-MST system in cancer biology. In many cancers (e.g. colon adenocarcinoma, lung adenocarcinoma, urothelial cell carcinoma, various forms of oral carcinomas), 3-MST is upregulated compared to the surrounding normal tissue. According to in vitro studies, 3-MST upregulation is especially prominent in cancer cells that recover from oxidative damage and/or develop a multidrug-resistant phenotype. Emerging data with newly discovered pharmacological inhibitors of 3-MST, as well as data using 3-MST silencing approaches suggest that the 3-MST/H2S system plays a role in maintaining cancer cell proliferation; it may also regulate bioenergetic and cell-signaling functions. Many questions remain open in the field of 3-MST/cancer biology; the last section of current article highlights these open questions and lays out potential experimental strategies to address them.

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KW - Angiogenesis

KW - Cell death

KW - Cell proliferation

KW - Cystathionine-β-synthases

KW - Cystathionine-γ-lyase

KW - Gasotransmitters

KW - Nitric oxide

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