Abstract 5990: The potential role of artificial lactate influx in remodeling cancer-specific metabolism of colorectal cancer

Abstract

Abstract Cancer cells have a specific metabolic pathway that produces a large quantity of lactate from glucose by abnormal aerobic glycolysis, it can provide a secondary path that meets the metabolic needs for persistent survival. Accordingly, regulating cancer-specific metabolism has important implications for the discovery of novel therapeutics. In this study, the possibility of an impact on colorectal cancer was investigated that focused on the remodeling of cancer-specific aerobic glycolysis by the artificial influx of lactate. Intracellular lactate levels were assessed in the colorectal cancer cells following lactate calcium salt treatment. Expression of lactate dehydrogenase and pyruvate dehydrogenase were confirmed to investigate the effect of the increased lactate influx. The nicotinamide adenine dinucleotide ratio and concentration of α-ketoglutarate were measured to confirm the tricarboxylic acid coupling. The tube formation and wound healing assay were performed as well as the expression of hypoxia-inducible factor-1α and vascular endothelial growth factor receptor to confirm the loss of malignancy. Xenograft animal models were established to evaluate the antitumor efficacy by monitoring changes in the tumor volume. We demonstrated that an artificial influx of lactate was increased in colon cancer cells under a hypoxic condition thereby reversible activation of lactate dehydrogenase reacting to lactate. Then, the conversion to pyruvate was promoted, and as a result of increased stimulation of pyruvate dehydrogenase, the tricarboxylic acid was coupled, showing an oxidative metabolism similar to normal cells. The malignancy of cancer cells was lost by undergoing remodeling of such cancer-specific, and a significant decrease in tumor growth was confirmed as a result of the anticancer effect of artificial lactate influx. These findings suggest the unique mechanisms in which the artificial influx of lactate would have anticancer effects by regulating cancer-specific aerobic glycolysis. Citation Format: Keun-Yeong Jeong. The potential role of artificial lactate influx in remodeling cancer-specific metabolism of colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5990.