Berberine Inhibits Human Neuroblastoma Cell Growth through Induction of p53-dependent Apoptosis

Abstract

Berberine, an alkaloid, has anti-tumor properties in some cancer cells, but action mechanisms are not clear yet. We here investigated the anticancer activity of berberine and possible mechanisms in human neuroblastoma SK-N-SH and SK-N-MC cells. The p53-expressing cells, SK-N-SH (IC₅₀=37 μM) were more susceptible to berberine than the p53-deficient cells, SK-N-MC (IC₅₀≥100 μM) without cytotoxic effect on the cortical neuronal cells. Berberine caused cell cycle arrest in G₀/G₁ phase and apoptotic cell death, and these effects were much greater in SK-N-SH cells than those in SK-N-MC cells. Berberine much greatly decreased G₀/G₁ phase-associated cyclin and cyclin-dependent kinase (cyclin D1, cyclin E, Cdk2, and Cdk4) expression, and increased apoptotic gene expression and activation of caspase-3 in SK-N-SH cells. Exploration of p53 siRNA or pifithrin-α (PFT-α), a p53 inhibitor, in the SK-N-SH cells resulted in increase of IC₅₀ values for cell viability, and decreased apoptotic cell death, expression of p53 and activation of caspase-3. Therefore, these results showed that berberine causes p53-dependent apoptotic death of neuroblastoma cells, and suggested that berberine may be useful as an anticancer agent for neuroblastoma.