Abstract 1855: Regulation of proliferation of colon cancer cells by compounds affecting glycolysis including 3-bromopyruvate, 2-deoxyglucose and biguanides

In earlier work we found that incubation of colon cancer cells with 2-deoxyglucose had an additive inhibitory effect on proliferation with the biguanides, metformin and phenformin, and blocked the acidification of the medium caused by incubation of cells with biguanides. In the present work, studies were performed with Caco-2, HCT116, HT29 and SW1116 colon cancer cells. Metabolism of glucose and acidification of the medium was greater with the more rapidly proliferating cells being greatest with HCT116 cells and least with SW1116 cells. We have seen that, as with 2-deoxyglucose, 3-bromopyruvate can also prevent the lowering of medium pH caused by biguanide treatment. . Inhibition of glucose metabolism paralleled the decrease in acidification of the medium. 3-bromopyruvate inhibited colon cancer cell proliferation. Additive effects with metformin and 3-bromopyruvate were not observed in any of the four colon cancer cell lines but some additive effects were seen with phenformin and 3-bromopyruvate. An additive effect was more notable in combined treatment with 3-bromopyruvate and 2-deoxyglucose. Induction of alkaline phosphatase activity serves as a marker of differentiation in colon cancer cells. The induction of alkaline phosphatase activity by butyrate was not consistently affected by combination with other agents that modified glucose metabolism. The drug combinations that were examined inhibited proliferation in wild type and P53 null HCT116 cells and affected colon cancer lines with different growth rates. Although metformin and phenformin increase glucose metabolism by colon cancer cells while 3-bromopyruvate and 2-deoxyglucose inhibit glucose metabolism, all these compounds have potential inhibitory action on the proliferation of colon cancer cells. Citation Format: Michael A. Lea, Mehreen Qureshi, Michael Buxhoeveden, Nicolette Gengel, Jessica Kleinschmit, Charles desBordes. Regulation of proliferation of colon cancer cells by compounds affecting glycolysis including 3-bromopyruvate, 2-deoxyglucose and biguanides. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1855. doi:10.1158/1538-7445.AM2013-1855