IDENTIFICATION OF A NOVEL SLOW-RELEASING HYDROGEN SULFIDE DONOR FOR CANCER THERAPY

Abstract

It has previously been reported that the slow-releasing hydrogen sulfide (H2S) donor, GYY4137, exerts anti-cancer activity both in vivo and in vitro. In this study, we identified an additional, slow-releasing H2S donor termed FW1010 (GYY4137 analogue). In biochemical studies, FW1010 released more H2S over a period of 6 days than did GYY4137. FW1010 also caused greater concentration-dependent killing of several human cancer cell lines than did GYY4137. This was brought about by apoptosis. Both GYY4137 and FW1010 significantly and concentration dependently increased glucose consumption and lactate production in cancer cells. FW1010 was more potent than GYY4137 in this regard. FW1010 and GYY4137 also concentration-dependently reduced intracellular pH (pHi) in cancer cells. Again FW1010 was more potent than GYY4137. Intriguingly, neither GYY4137 nor FW1010 affected cell death, glucose consumption, lactate production or pHi in a normal (i.e. non-cancer) cell line. These experiments identify a new GYY4137 analogue with seemingly greater potency.