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

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• 作者：Debbie M. Gurfinkel ; Sue Chow ; Rose Hurren ; Marcela Gronda ; Clare Henderson ; Christina Berube ; David W. Hedley and Aaron D. Schimmer
• 关键词：Asiatic acid ; Triterpenoids ; Endoplasmic reticulum ; Caspase ; 2 ; Calcium
• 刊名：Apoptosis
• 出版年：2006
• 出版时间：September, 2006
• 年：2006
• 卷：11
• 期：9
• 页码：1463-1471
• 全文大小：517 KB
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  Cancer Research
  Cell Biology
  Biochemistry
  Virology
  
• 出版者：Springer Netherlands
• ISSN：1573-675X

文摘

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.