6 ′ -O-Galloylpaeoniflorin Exerts Inhibitory Bioactivities in Human Neuroblastoma Cells via Modulating AMPK/miR-489/XIAP Pathway

Abstract

Although therapies against neuroblastoma (NBM) have advanced, the patients still suffer from poor prognoses due to distal metastasis or the occurrence of multidrug resistance. Accumulating evidence has proved that chemicals derived from natural products possess potent anti-NBM properties or can be used as adjuvants for chemotherapy. In the present study, we demonstrated that 6 ${}^{\prime }$ -O-galloylpaeoniflorin (GPF), a galloylated derivative of paeoniflorin isolated from the roots of Paeonia lactiflora Pall, exerted significant inhibitory effects on proliferation and invasion of SH-SY5Y cells (an NBM cell line) and enhanced the sensitivity of SH-SY5Y cells to cisplatin in vitro. Further studies showed that GPF treatment upregulated miR-489 in NBM cells via activating AMP-activated protein kinase (AMPK). We also demonstrated that similar to GPF treatment, miR-489 exhibited a significant anti-NBM capacity. Further studies showed that miR-489 directly targeted the X-linked inhibitor of apoptosis protein (XIAP). Overall, our results indicated that GPF possessed an evident anti-NBM capacity dependent on AMPK/miR-489/XIAP pathway, providing an emerging strategy for clinical treatment of NBM.