Induction of apoptosis by FFJ-5, a novel naphthoquinone compound, occurs via downregulation of PKM2 in A549 and HepG2 cells

Pyruvate kinase isoenzyme M2 (PKM2) has previously been identified as a tumor biomarker and as a potential target for cancer therapy. In this study, F§FJ-5, a characterized naphthoquinone modifier of mollugin, was synthesized in order to investigate its anticancer activity and the potential mechanisms. It was observed that FFJ-5 inhibited the cell growth of human lung adenocarcinoma cells A549 and human hepatoma cells HepG2 by MTT assays. FFJ-5 arrested cell cycle at the G2/M phase. Further analyses demonstrated that FFJ-5 attenuated the expression of PKM2 and reduced the production of adenosine triphosphate (ATP). Reduced expression and activity of epidermal growth factor receptor (EGFR) and Akt were observed in A549 and HepG2 cells exposed to FFJ-5. FFJ-5 exposure also resulted in cell apoptosis, in association with decreased intracellular pH level and mitochondrial membrane potential. In addition, FFJ-5 activated the caspase-3 cascade. In conclusion, FFJ-5 inhibited cancer cell growth via the blocking the EGFR-Akt-PKM2 pathway or through the synergistic action of EGFR, Akt and PKM2 proteins, alongside a decrease in ATP production. In addition, FFJ-5 induced cancer cell apoptosis by decreasing the intracellular pH level and the mitochondrial apoptosis pathway. The present results suggest a potential role of FFJ-5 on the therapy of human cancer.