In vitro effects of some flavonoids and phenolic acids on human pyruvate kinase isoenzyme M2

Abstract

Pyruvate kinase isoenzyme M2 (PKM2) is one of the most important control point enzyme in glycolysis pathway. Hence, its inhibitors and activators are currently considered as the potential anticancer agents. The effect of 28 polyphenolic compounds on the enzyme activity was investigated in vitro. Among these compounds, neoeriocitrin, (−)-catechin gallate, fisetin, (±)-taxifolin and (−)-epicatechin have the highest inhibition effect with IC₅₀ value within 0.65–1.33 µM range. Myricetin and quercetin 3-β-d-glucoside exhibited the highest activation effect with 0.51 and 1.34 µM AC₅₀ values, respectively. Twelve of the compounds showed inhibition effect within 7–38 µM range of IC₅₀ value. Sinapinic acid and p-coumaric acid showed an activation effect with 26.2 and 22.2 µM AC₅₀ values, respectively. The results propose that the polyphenolics may be the potential PKM2 inhibitors/activators, and they may be used as lead compounds for the synthesis of new inhibitors or activators of this enzyme.

• Activation
• cancer
• flavonoid
• inhibition
• phenolic acid
• PKM2

Declaration of interest

This research was financed by TUBITAK (Project No: 112T781).