Abstract 4069: 2-deoxyglucose and compound C reversed acidification but enhanced growth inhibition in colon cancer cells treated with metformin and phenformin

Abstract

Abstract A report that effects of butyrate on some cells may be mediated by activation of AMP-dependent kinase (AMPK) prompted us to examine if other AMPK activators can induce differentiation and inhibit proliferation of colon cancer cells in a manner similar to butyrate. Using induction of alkaline phosphatase as a marker, we observed that compound C, an AMPK inhibitor, could decrease the differentiating effect of butyrate or valproate on SW1116 and Caco-2 colon cancer cells. On the other hand, A769662, an activator of AMPK did not increase alkaline phosphatase activity and decreased the induction seen with butyrate. Metformin was observed to be less effective than butyrate in the induction of alkaline phosphatase but was more effective as a growth inhibitor. Phenformin was found to be a more potent growth inhibitor than metformin and both compounds cause acidification of the medium when incubated with colon cancer cells. pH changes were monitored with a pH electrode and by the decrease in absorbance of phenol red at 560 nm. Coincubation with compound C decreased the acidification caused by the biguanides. Combined incubation of 2-deoxyglucose with either of the biguanides prevented the acidification of the medium but enhanced the growth inhibitory effects. Growth inhibitory effects of biguanides appeared less with a tetrazolium reduction assay than with thymidine incorporation but supported the conclusion that combination with 2-deoxyglucose could increase growth inhibition caused by biguanides. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4069. doi:10.1158/1538-7445.AM2011-4069