Project Details
Projekt
Impact of archazolid on tumor metabolism
Applicant
Dr. Karin von Schwarzenberg
Subject Area
Pharmacy
Term
from 2014 to 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 159663715
A century ago Otto Warburg made the finding that tumor cells utilize glycolysis instead of mitochondrial oxidative phosphorylation for glucose metabolism even in the presence of oxygen. Extensive research in this field showed that aerobic glycolysis is advantageous for the tumor cells as they can use glucose not only as ATP source but also as building blocks for essential metabolites like fatty acids and amino acids which they need for proliferation. A glycolytic switch is promoted by the hypoxic areas occurring in tumors but also by mutations in mitochondria and especially promoted by oncogenes. Due to the distinct metabolism of tumor cells targeting its pathways or resources has come into focus in cancer therapy. During the first funding period we could show that inhibition of the V-ATPase by the myxobacterial compound archazolid not only leads to apoptosis induction but also induced the transcription of genes related to glycolysis, fatty acid and cholesterol synthesis. Furthermore we found an increased consumption of glucose and a strong induction of HIF1α which suggests an alteration in metabolism. Here we aim to analyze the reason for alterations in tumor metabolism as well as the consequences for the cell and are aiming to find specific pathways to therapeutically interfere especially using drug combinations. We furthermore want to investigate the potential of archazolid in in vivo models aiming to use combinations that target different steps in metabolic pathways.
DFG Programme
Research Units
