Disruption of the endoplasmic reticulum and increases in cytoplasmic calcium are early events in cell death induced by the natural triterpenoid Asiatic acid

Apoptosis. 2006 Sep;11(9):1463-71. doi: 10.1007/s10495-006-9086-z.


Triterpenoids are a novel class of compounds being investigated as potential therapeutic agents for the treatment of prostate cancer and other malignancies. Asiatic acid (AA) is a member of the ursane family of triterpenoids and has anticancer activity, but its mechanism of action is not completely understood. To investigate its mechanism of action, PPC-1 prostate cancer cells were treated with AA at increasing concentrations and times. AA induced rapid caspase-dependent and independent cell death that peaked within 8 h of treatment. AA-induced death was associated with early activation of caspases 2, 3, and 8, but not caspase 9. Within 2.5 h of treatment, release of calcium from intracellular stores and dilatation of the endoplasmic reticulum was observed. Thus, disruption of the endoplasmic reticulum and alterations in calcium homeostasis are early events in AA-induced death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Caspase 2 / metabolism
  • Caspase 3 / metabolism
  • Caspases / metabolism
  • Cell Death / drug effects*
  • Cell Survival
  • Cytoplasm / chemistry
  • Cytoplasm / metabolism
  • Drug Resistance, Neoplasm
  • Endoplasmic Reticulum / drug effects*
  • Humans
  • Lethal Dose 50
  • Male
  • Mice
  • Models, Biological
  • Pentacyclic Triterpenes
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / metabolism
  • Triterpenes / pharmacology*
  • Triterpenes / therapeutic use
  • Tumor Cells, Cultured


  • Pentacyclic Triterpenes
  • Triterpenes
  • asiatic acid
  • Caspase 2
  • Caspase 3
  • Caspases
  • Calcium