S6-5 Role of cystathionine-beta synthase and its product, hydrogen sulfide in cancer biology

In colorectal and ovarian cancer, increased production of hydrogen sulfide (H2S) from cystathionine-β-synthase (CBS) plays an important role in promoting cellular bioenergetics, proliferation and migration. Pharmacological inhibition or genetic silencing of CBS exerts antitumor effects in vitro and in vivo, and potentiates the efficacy of current standard-of-care anticancer therapeutics. In this four-part presentation, we will first summarize recently published studies documenting a critical role for CBS-dependent H2S production in cancer cell proliferation and tumorigenesis. Second, we will discuss the state-of-the-art of CBS activity modulation with special reference to allosteric CBS activators (such as S-adenosylmethionine) and pharmacological CBS inhibitors of various classes including the complex pharmacology of aminooxyacetic acid. Third, we will present new experimental evidence designed to reconcile a controversy in the literature regarding the apparently contradictory effects of H2S donors on cancer cell proliferation and survival. Finally, we will discuss current and future strategies for targeting cancer cell H2S-production in the development of novel anticancer therapies.