A Novel Pyruvate Kinase M2 Activator Compound that Suppresses Lung Cancer Cell Viability under Hypoxia

• DOI: 10.14348/molcells.2015.2314
• Publication Date: 2015-03-28T18:07:36Z
• Authors: Dong Joon Kim; Young Soo Park; Nam Doo Kim; Sang Hyun Min; Yeon-Mi You; Yuri Jung; Han Koo; Hanmi Noh; Jung-Ae Kim; Kyung Chan Park; Young Il Yeom
• Keywords: PKM2; Viability assay

Pyruvate kinase M2 isoform (PKM2), a rate-limiting enzyme in the final step of glycolysis, is known to be associated with metabolic rewiring cancer cells, and considered an important therapeutic target. Herein, we report novel PKM2 activator, PA-12, which was identified via molecular docking-based virtual screening. We demonstrate that PA-12 stimulates pyruvate activity recombinant vitro, half-maximal concentration 4.92 μM, effectively suppresses both anchorage-dependent -independent growth lung cells non-essential amino acid-depleted medium. In addition, blocked nuclear translocalization resulting inhibition hypoxia response element (HRE)-mediated reporter as well hypoxia-inducible factor 1 (HIF-1) target gene expression, eventually leading suppression cell viability under hypoxia. also verified effects were dependent on expression demonstrating specificity for protein. Taken together, our data suggest potent activator has implications cancer.