LAUSR

Multiple myeloma (MM) cells are characterized by an abnormal nutrient metabolism that is distinct from normal plasma cells. Pterostilbene (PTE), a bioactive component of blueberries, has been demonstrated to induce apoptosis in multiple types of cancer cell. The present study evaluated whether PTE treatment affected the survival of MM cells from a metabolic perspective, and the potential mechanisms of this. It was observed that the administration of PTE induced apoptosis, which was mediated by the increased activation of AMP-activated protein kinase (AMPK). Once activated, AMPK decreased the expression and/or activity of key lipo-genic enzymes, including fatty acid synthase and acetyl-CoA carboxylase. In addition, the activation of AMPK suppressed the downstream substrate, mechanistic target of rapamycin, which dephosphorylated eukaryotic initiation factor 4E-binding protein 1, leading to a general decrease in mRNA translation. Pre-treatment with the AMPK inhibitor compound C prior to PTE treatment compromised the anti-myeloma apoptosis effect, suggesting the critical role of AMPK in mediating PTE-induced cell toxicity. Consistent results were obtained in vivo. Finally, autophagy was adaptively upregulated subsequent to PTE treatment; the pro-apoptotic efficacy of PTE was potentiated once autophagic flux was inhibited by 3-methyladenine. Taken together, these data demonstrated that PTE exerts anti-tumor effects on MM cells via AMPK-induced nutrient suppression.