The therapeutic potential of cystathionine β-Synthetase/hydrogen sulfide inhibition in cancer

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Significance: Cancer represents a major socioeconomic problem; there is a significant need for novel therapeutic approaches targeting tumor-specific pathways. Recent Advances: In colorectal and ovarian cancers, an increase in the intratumor production of hydrogen sulfide (H2S) from cystathionine β-synthase (CBS) plays an important role in promoting the cellular bioenergetics, proliferation, and migration of cancer cells. It also stimulates peritumor angiogenesis inhibition or genetic silencing of CBS exerts antitumor effects both in vitro and in vivo, and potentiates the antitumor efficacy of anticancer therapeutics. Critical Issues: Recently published studies are reviewed, implicating CBS overexpression and H2S overproduction in tumor cells as a tumor-growth promoting "bioenergetic fuel" and "survival factor," followed by an overview of the experimental evidence demonstrating the anticancer effect of CBS inhibition. Next, the current state of the art of pharmacological CBS inhibitors is reviewed, with special reference to the complex pharmacological actions of aminooxyacetic acid. Finally, new experimental evidence is presented to reconcile a controversy in the literature regarding the effects of H2S donor on cancer cell proliferation and survival. Future Directions: From a basic science standpoint, future directions in the field include the delineation of the molecular mechanism of CBS up-regulation of cancer cells and the delineation of the interactions of H2S with other intracellular pathways of cancer cell metabolism and proliferation. From the translational science standpoint, future directions include the translation of the recently emerging roles of H2S in cancer into human diagnostic and therapeutic approaches. Antioxid. Redox Signal. 22, 424-448.

Original languageEnglish (US)
Pages (from-to)424-448
Number of pages25
JournalAntioxidants and Redox Signaling
Volume22
Issue number5
DOIs
StatePublished - Feb 10 2015

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Cystathionine beta-Synthase
Hydrogen Sulfide
Cells
Tumors
Neoplasms
Cystathionine
Aminooxyacetic Acid
Cell proliferation
Therapeutics
Cell Proliferation
Metabolism
Energy Metabolism
Pharmacology
Direction compound
Cell Communication
Ovarian Neoplasms
Oxidation-Reduction
Cell Movement
Colorectal Neoplasms
Cell Survival

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Physiology
  • Clinical Biochemistry

Cite this

The therapeutic potential of cystathionine β-Synthetase/hydrogen sulfide inhibition in cancer. / Hellmich, Mark; Coletta, Ciro; Chao, Celia; Szabo, Csaba.

In: Antioxidants and Redox Signaling, Vol. 22, No. 5, 10.02.2015, p. 424-448.

Research output: Contribution to journalArticle

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