Xing Wang, You-Zhen Wei
Apr 15, 2010
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Cancer Research
Abstract
In general, mutations in oncogenes and tumor suppressor genes are believed to represent the fundamental cause of carcinogenesis. Mitochondrial deficiency (Warburg effect) may be a direct or indirect consequence of these mutations. Accordingly, tumor cells depend on glycolysis rather than mitochondrial oxidative metabolism as energy source for their survival and proliferation. Targeting this kind of metabolism could offer a possibility for cancer treatment. Erythrose was used as an alternative energy source to test its inhibitory effect on several tumor cell lines in vitro and in vivo. Cancer cell lines (breast BT474 and MCF-7, brain U87mg, pancreas Panc-1, HEL, LL-2 Lewis lung, and colorectal CT26 and SW480 lines) were grown in DMEM + 10% FBS media with different concentrations of D-erythrose and cell growth was tested with the Trypan blue assay. In general, 70% of cancer cells did not survive after 24 hrs of culture with 500mg/L D-erythrose. Addition of ZnCl2 (40µM) doubled the cancer killing effect at 400mg/L D-erythrose. In addition, LL-2 Lewis lung cells were subcutaneously introduced into the immunocompetent C57BL/6 mice. After allowing tumor growth to 2.7±0.4mm wide diameters, a daily subcutaneous injection beside the tumor with D-erythrose (∼1g/kg bw) was administered for 25 days; controls received a PBS injection instead. Tumor growth in erythrose-treated mice was inhibited more than 90% by weight. We hypothesize that the administration of erythrose leads to CO2 production from oxidation in cytosol or mitochondria. Carbonic acid is formed from CO2 and water, accelerated by carbonic anhydrase (a zinc enzyme), which can convert lactate to lactic acid, and cause intracellular acidosis and cancer death since cancer cells have increased lactate production. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4548.