Cinnamic acid derivative reduces tumor growth by decreasing Hif-1α expression and suppressing the Warburg effect

Abstract

Background. Tumor growth is characterized by the presence of specific features that can be the basis for rational treatment. One of these features is the Warburg paradox, which manifests itself in the prevalence of glycolytic oxidation reactions over aerobic metabolism at adequate intracellular oxygen concentrations. Purpose. Under experimental conditions, to evaluate the possibility of correcting metabolic glycolytic abnormalities of tumor cells through course therapy with 4-hydroxy-3,5-di-tretbutyl cinnamic acid. Materials and methods. The study was performed on male Wistar rats, in which tumor cells of the C6-BU-1 line were implanted in the brain. The test compound 4-hydroxy3,5-di-tret butyl cinnamic acid and reference resveratrol were administered per os at doses of 100 mg/kg and 20 mg/kg, respectively, for 14 days from the moment of tumor inoculation. After the specified time, the rats were decapitated, the tumor tissue was extracted. In the course of the work, the volume of the tumor, the activity of ana/aerobic reactions of cellular metabolism, changes in mitochondrial biogenesis and the concentration of Hif-1a were determined. Results. The study showed that the course administration of resveratrol and 4-hydroxy3,5-di-tret butyl cinnamic acid contributed to a decrease in tumor volume compared to untreated animals by 22.9 % (p < 0.05) and 34.3 % (p < 0.05), respectively. Also, against the background of the use of the studied compound, there was a decrease in the content of Hif-1a by 27.4 % (p < 0.05), respectively, an increase in the activity of the enzymatic markers of mitochondrial biogenesis – succinate dehydrogenase and cytochrome-c oxidase by 166.7 % (p < 0.05) and 125.0 % (p < 0.05). The intensity of anaerobic metabolic reactions in rats treated by the test compound and resveratrol was significantly lower than in untreated rats, while the activity of aerobic processes considerably increased. Conclusion. The study showed that the administration of 4-hydroxy-3,5-di-tret butyl cinnamic acid reduces the intensity of anaerobic metabolism in tumor cells by reducing the expression of Hif-1a, which in turn suppresses tumor growth.