Pterostilbene inhibits nutrient metabolism and induces apoptosis through AMPK activation in multiple myeloma cells

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.