Cotreatment with dichloroacetate and omeprazole exhibits a synergistic antiproliferative effect on malignant tumors

Abstract

It has been reported that treating cancer cells with dichloroacetate (DCA), an approved treatment for congenital lactic acidosis, reverses the Warburg effect and inhibits tumor growth). Furthermore, omeprazole (OMP) is a well-known agent that enhances the effects of anticancer drugs. The aim of this study was to find clinically-used drugs that enhance the effects of DCA. The combination of DCA and OMP exhibited a more potent antitumor activity than DCA alone in HT1080 fibrosarcoma cells and RKO colon cancer cells, while the drugs did not affect the proliferation of WI-38 human fibroblasts. The inhibitory effect of DCA combined with OMP was reversed with vitamin E and Z-VAD-FMK; therefore conventional caspase-dependent cell growth inhibition through superoxide production was suggested as the mechanism for inhibition. The combination of these drugs also had an effect on HT1080 fibrosarcoma cells inoculated into mice. Since OMP and DCA may be administered orally and have been used clinically for several years without major side effects, we believe that this combination therapy could be readily translated to treat malignant tumors.