科研之友
微信
新浪微博
Facebook
分享链接
摘要
Apigenin (AP), as an anticancer agent, has been widely explored. However, the molecular targets of apigenin on tumor metabolism are unclear. Herein, we found that AP could block cellular glycolysis through restraining the tumor -specific pyruvate kinase M2 (PKM2) activity and expression and further significantly induce anti -colon cancer effects. The IC50 values of AP against HCT116, HT29, and DLD1 cells were 27.9 +/- 2.45, 48.2 +/- 3.01 and 89.5 +/- 4.89 mu m,respectively. Fluorescence spectra and solid-phase AP extraction assays proved that AP could directly bind to PKM2 and markedly inhibit PKM2 activity in vitro and in HCT116 cells. Interestingly, in the presence of D-fructose-1,6-diphosphate (FBP), the inhibitory effect of AP on PKM2 was not reversed, which suggests that AP is a new allosteric inhibitor of PKM2. RT-PCR and Western blot assays showed that AP could ensure a low PKM2/PKM1 ratio in HCT116 cells via blocking the,beta-catenin/c-Myc/PTBP1 signal pathway. Hence, PKM2 represents a novel potential target of AP against colon cancer.
