Ginsenoside Rh2 induces apoptosis and paraptosis-like cell death in colorectal cancer cells through activation of p53

Cancer Lett. 2011 Feb 28;301(2):185-92. doi: 10.1016/j.canlet.2010.11.015. Epub 2010 Dec 30.


Ginsenosides are the main bioactive components in American ginseng, a commonly used herb. In this study, we showed that the ginsenoside Rh2 exhibited significantly more potent cell death activity than the ginsenoside Rg3 in HCT116 and SW480 colorectal cancer cells. Cell death induced by Rh2 is mediated in part by the caspase-dependent apoptosis and in part by the caspase-independent paraptosis, a type of cell death that is characterized by the accumulation of cytoplasmic vacuoles. Treatment of cells with Rh2 activated the p53 pathway and significantly increased the levels of the pro-apoptotic regulator, Bax, while decreasing the levels of anti-apoptosis regulator Bcl-2. Removal of p53 significantly blocked Rh2-induced cell death as well as vacuole formation, suggesting that both types of cell death induced by Rh2 are mediated by p53 activity. Furthermore, we show that Rh2 increased ROS levels and activated the NF-κB survival pathway. Blockage of ROS by NAC or catalase inhibited the activation of NF-κB signaling and enhanced Rh2-induced cell death, suggesting that the anti-cancer effect of Rh2 can be enhanced by antioxidants.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylcysteine / pharmacology
  • Amino Acid Chloromethyl Ketones / pharmacology
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Blotting, Western
  • Caspase Inhibitors
  • Caspases / metabolism
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Cysteine Proteinase Inhibitors / pharmacology
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / pharmacology
  • Free Radical Scavengers / pharmacology
  • Ginsenosides / pharmacology*
  • HCT116 Cells
  • HEK293 Cells
  • Humans
  • Mutation
  • NF-kappa B / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Vacuoles / drug effects
  • Vacuoles / metabolism


  • Amino Acid Chloromethyl Ketones
  • Apoptosis Regulatory Proteins
  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors
  • Drugs, Chinese Herbal
  • Free Radical Scavengers
  • Ginsenosides
  • NF-kappa B
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • ginsenoside Rg3
  • ginsenoside Rh2
  • Caspases
  • Acetylcysteine