Ginsenoside Compound K Induces Ros-Mediated Apoptosis and Autophagic Inhibition in Human Neuroblastoma Cells In Vitro and In Vivo

Int J Mol Sci. 2019 Sep 1;20(17):4279. doi: 10.3390/ijms20174279.


Autophagy can result in cellular adaptation, as well as cell survival or cell death. Modulation of autophagy is increasingly regarded as a promising cancer therapeutic approach. Ginsenoside compound K (CK), an active metabolite of ginsenosides isolated from Panax ginseng C.A. Meyer, has been identified to inhibit growth of cancer cell lines. However, the molecular mechanisms of CK effects on autophagy and neuroblastoma cell death have not yet been investigated. In the present study, CK inhibited neuroblastoma cell proliferation in vitro and in vivo. Treatment by CK also induced the accumulation of sub-G1 population, and caspase-dependent apoptosis in neuroblastoma cells. In addition, CK promotes autophagosome accumulation by inducing early-stage autophagy but inhibits autophagic flux by blocking of autophagosome and lysosome fusion, the step of late-stage autophagy. This effect of CK appears to be mediated through the induction of intracellular reactive oxygen species (ROS) and mitochondria membrane potential loss. Moreover, chloroquine, an autophagy flux inhibitor, further promoted CK-induced apoptosis, mitochondrial ROS induction, and mitochondria damage. Interestingly, those promoted phenomena were rescued by co-treatment with a ROS scavenging agent and an autophagy inducer. Taken together, our findings suggest that ginsenoside CK induced ROS-mediated apoptosis and autophagic flux inhibition, and the combination of CK with chloroquine, a pharmacological inhibitor of autophagy, may be a novel therapeutic potential for the treatment of neuroblastoma.

Keywords: apoptosis; autophagy; ginsenoside; mitochondrial ROS; neuroblastoma.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Ginsenosides / pharmacology*
  • Ginsenosides / therapeutic use
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Mice
  • Mice, Nude
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / metabolism
  • Neuroblastoma / physiopathology
  • Reactive Oxygen Species / metabolism*
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents
  • Ginsenosides
  • Reactive Oxygen Species
  • ginsenoside M1