The Therapeutic Potential of Cystathionine β-Synthetase/Hydrogen Sulfide Inhibition in Cancer

<jats:p> <jats:bold> <jats:italic toggle="yes">Significance:</jats:italic> </jats:bold> Cancer represents a major socioeconomic problem; there is a significant need for novel therapeutic approaches targeting tumor-specific pathways. <jats:bold> <jats:italic toggle="yes">Recent Advances:</jats:italic> </jats:bold> In colorectal and ovarian cancers, an increase in the intratumor production of hydrogen sulfide (H <jats:sub>2</jats:sub> S) 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 <jats:italic toggle="yes">in vitro</jats:italic> and <jats:italic toggle="yes">in vivo</jats:italic> , and potentiates the antitumor efficacy of anticancer therapeutics. <jats:bold> <jats:italic toggle="yes">Critical Issues:</jats:italic> </jats:bold> Recently published studies are reviewed, implicating CBS overexpression and H <jats:sub>2</jats:sub> S 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 H <jats:sub>2</jats:sub> S donor on cancer cell proliferation and survival. <jats:bold> <jats:italic toggle="yes">Future Directions:</jats:italic> </jats:bold> 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 H <jats:sub>2</jats:sub> S 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 H <jats:sub>2</jats:sub> S in cancer into human diagnostic and therapeutic approaches. <jats:italic toggle="yes">Antioxid. Redox Signal</jats:italic> . 22, 424–448. </jats:p>