title: The therapeutic potential of cystathionine β-synthetase/hydrogen sulfide inhibition in cancer.
abstract: CONCLUSIONS
  Cancer represents a major socioeconomic problem; there is a significant need for novel therapeutic approaches targeting tumor-specific pathways.
  
  
  BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1 Department of Surgery, University of Texas Medical Branch , Galveston, Texas.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Hellmich
authors.forename: Ciro
authors.initials: C
authors.lastname: Coletta
authors.forename: Celia
authors.initials: C
authors.lastname: Chao
authors.forename: Csaba
authors.initials: C
authors.lastname: Szabo
mesh_terms: D000625:Aminooxyacetic Acid / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D003541:Cystathionine beta-Synthase / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D006801:Humans; D006862:Hydrogen Sulfide / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000625:Aminooxyacetic Acid; D003541:Cystathionine beta-Synthase; D006862:Hydrogen Sulfide
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