Abstract 1169: Growth regulation of bladder cancer cells by compounds that affect glucose metabolism

Abstract

Abstract The observation that cancer cells tend to exhibit enhanced rates of glycolysis presents a target for therapeutic regulation of cancer cell growth by molecules that regulate glucose metabolism. We have extended our earlier studies on colon cancer cells with an examination in bladder cancer cells of the action of an established inhibitor of PFKFB3, namely 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) as a single agent and in combination with other molecules that affect glycolysis and proliferation. 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB-3) is an enzyme regulating glycolysis in many tumor cells. Cell growth was monitored by staining with sulforhodamine B. Of the 8 cell lines examined, growth was most rapid in the T24 and UM-UC-3 bladder cancer cells. The slowest growth was seen with RT4, TCCSUP and HT1197 cells while intermediate growth rates were observed with 5637, HT1376, and SW780 cells. Glucose uptake from the medium and acidification of the medium over a 72-hour incubation tended to correlate with growth rate. Thus the greatest changes were seen with the T24 and UM-UC-3 cell lines and the least change was seen with RT4 and TCCSUP cells. Growth was inhibited when glutamine was omitted from the medium but growth was blocked in the absence of glucose except for RT4 cells in which growth was inhibited more in the absence of glutamine. Treatment with 10 μM 3PO as a single agent for 72 hours caused average growth inhibition in the range of 25-50% without apparent relationship to the control growth rates of the cell lines. Additive inhibitory effects on growth were observed when cells were coincubated with 3PO and either 1 mM 2-deoxyglucose, 50 μM phenformin or 1 mM butyrate. In addition to being growth inhibitory, butyrate also caused significant induction of alkaline phosphatase activity in some cell lines. When cells were incubated with phenformin as a single agent, there was generally an increased acidification of the medium that was diminished by coincubation with 3PO. In conclusion, 3PO was an inhibitor of proliferation of human bladder cancer cells and may be a useful agent in combination with other drugs that inhibit bladder cancer cell proliferation. Citation Format: Michael A. Lea, Charles desBordes. Growth regulation of bladder cancer cells by compounds that affect glucose metabolism. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1169. doi:10.1158/1538-7445.AM2015-1169