Ginsenoside Rk1 Induces Apoptosis in Neuroblastoma Cells Through Loss of Mitochondrial Membrane Potential and Activation of Caspases

Abstract

Neuroblastoma (NB) is the most common childhood cancer, with a very poor prognosis. More than 60% of children with NB die within five years; therefore, a more effective therapy for NB is required. Although ginsenoside has been shown to significantly inhibit the growth of various cancers, the effect of ginsenoside Rk1 on neuroblastoma has not been known yet. Hence, we examined the anticancer effects of highly pure Rk1 on neuroblastoma cell lines. The apoptotic effects of Rk1 on neuroblastoma cells were examined using cell viability assay, flow cytometry and cell staining assay, and the change in gene expression levels were analysed using RT-PCR, western blots, and immunohistochemistry. The metastatic effect of Rk1 was monitored by wound healing assay, invasion and migration with Matrigels. Rk1 inhibited neuroblastoma cell viability dose-dependently. Rk1-induced apoptosis was investigated through nuclear condensation and mitochondrial membrane potential loss, and it showed that Rk1 can induce cell cycle arrest at the G0/G1 phase but also inhibit the metastatic ability of neuroblastoma cells. Moreover, Rk1 (30 mg/kg) injections markedly inhibited xenograft tumor growth. These findings demonstrate that Rk1 might be valuable in the development of anti-cancer agents for neuroblastoma treatment.