Effects of polyphenols/flavonoids on the metabolic sensitivity of the cell: cellular mechanisms and relevance in vitro and in vivo

• Applicant: Privatdozent Dr. Karlis Briviba
• Subject Area: Nutritional Sciences
• Term: from 2007 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 35674991

The flavonol, quercetin and the catechin epigallocatechin-3-gallate (EGCG) have been shown to represent potential bioactive compounds modulating activity and transcription of key enzymes of the glucose/glycogen homeostasis. Down-regulation of the brain-type glycogen phosphorylase, an early biomarker in colon carcinogenesis, by EGCG recommend further investigation on the mechanisms involved in the chemopreventive activity of this compound. The altered metabolic pattern observed in the glycolytic phenotype of highly proliferating cancer cells confers a common advantage allowing cell survival and invasion. The modulation of glucose homeostasis in the glycolytic phenotype of invasive cancer cells implicates a promising way of suppressing tumor growth and invasion. A major goal of the project is to investigate the impact of bioactive flavonoids on cellular glucose homeostasis in in vitro and in vivo with emphasis on glycolysis and gluconeogenesis. The question will be addressed whether there are targets affected such as glycogen phosphorylase which might be of relevance for tumor cell survival of the glycolytic phenotype and for cellular glucose homeostasis relevant in diabetes mellitus. As EGCG has been identified as a potent GP inhibitor in vitro, the role of EGCG in carbohydrate metabolism and carcinogenesis will be investigated in vivo. A deeper insight into mechanisms involved in the chemopreventive activity of flavonoids especially of EGCG is expected contributing to a better benefit/risk evaluation of flavonoids.

• DFG Programme: Research Grants
• Participating Person: Professorin Dr. Doris Marko