A PKM2 inhibitor induces apoptosis and autophagy through JAK2 in human oral squamous cell carcinoma cells

The enzyme pyruvate kinase M2 (PKM2) is involved in glycolysis, which plays an important role in the regulation of tumor progression. In this study, we investigated the anti-tumor activity of N-(4-(3-(3-(methylamino)-3-oxopropyl)-5-(4 '-(trifluoromethyl)-[1,1 '-biphenyl]-4-yl)-1H-pyrazol-1-yl)phenyl)propiolamide (MTP), a PKM2 inhibitor, in oral squamous cell carcinoma (OSCC) cells. Our results showed that MTP inhibited cell growth with IC50 values of 0.59 mu M and 0.78 mu M in SCC2095 and HSC-3 OSCC cells, respectively. MTP induced caspase-dependent apoptosis, which was associated with the modulation of PKM2 and oncogenic biomarkers epidermal growth factor receptor and beta-catenin. In addition, MTP increased the generation of reactive oxygen species (ROS) and modulated the expression of autophagic gene products, including LC3B-II and p62. Western blotting showed that MTP inhibited Janus kinase 2 (JAK2) signaling, and JAK2 overexpression partially reversed MTP-mediated cytotoxicity. Taken together, these data indicate the potential use of MTP as a therapeutic agent for OSCC.

Automated summary

This study investigated the anti-tumor activity of a PKM2 inhibitor called MTP in oral squamous cell carcinoma cells. The results showed that MTP inhibited cell growth, induced apoptosis, and modulated the expression of PKM2 and oncogenic biomarkers. In addition, MTP increased reactive oxygen species generation and affected the expression of autophagic genes. These findings suggest that MTP has potential therapeutic use for oral squamous cell carcinoma.