Investigate of effects of some polyphenol compounds on pyruvate kinase isoenzyme M2 activity

Metabolic regulation in rapidly growing tissues such as fetal tissues and tumours is different from that in most adult tissues. One of the most prominent distinctions between healthy and cancerous tissues is the differing energetic and nutritional needs associated with the rapid proliferative nature of cancer cells. In cancer cells glycolysis frequently is increased for generation of ATP to meet their energy needs. Also one or more isoforms of glycolytic enzymes have altered expression patterns or activities in cancer cells. It is option that enzymatic mutation in the tumor cells could be used as a potential target for cancer chemotherapy. In the cancer cells are characterized by an over expression of the pyruvat kinase isoenzyme type M2 (PKM2) which plays a key role in the glycolytic pathway. PKM2 is a master switch orienting glycolysis to ATP synthesis or to the production of biosynthetic blocks. For this reason it is an important target for anticancer treatments. PKM2 inhibitors and activators can be used as chemotherapeutic drug or combining chemotherapeutic drug to overcome drug resistance. As such, the discovery of new inhibitors/activators for his enzyme is very significant. In this study was investigated the effects on PKM2 enzyme activity of 1 7 phenolic compounds. Inhibition strength of compounds were identified by calculating IC50 and Ki values for substances that showed inhibition effects on this enzyme activity. IC50 values were calculated for substances that show activition effects. Enzyme activity was assayed by converting from NADH to NAD+ using lactate dehydrogenase(LDH) resulting in a decrease in absorbance at 340 nm. Key Words: Pyruvat kinase M2 inhibitor, activator, cancer