A natural inhibitor of kidney-type glutaminase: a withanolide from Physalis pubescens with potent anti-tumor activity.

ABSTRACT: Kidney-type glutaminase (KGA), a mitochondrial enzyme converting glutamine to glutamate for energy supply, was over-expressed in many cancers and had been regarded as a promising therapeutic target in recent years. Structure-based virtual ligand screening predicted physapubescin K, a new withanolide from Physalis pubescens, to be potential KGA inhibitor. Enzyme activity inhibition assays and microscale thermophoresis experiments had demonstrated the efficiency and specificity of physapubescin K targeting KGA. Additionally, physapubescin K exhibited potent proliferation inhibitory effects on a panel of human cancer cell lines, such as SW1990 and HCC827-ER. It blocked glutamine metabolism in SW1990 with increasing intracellular level of glutamine and decreasing glutamate and its downs

SUBMITTER: Wu C 

PROVIDER: S-EPMC5768343 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature