Disruption of the endoplasmic reticulum and increases in cytoplasmic calcium are early events in cell death induced by the natural triterpenoid Asiatic acid.
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.
Gurfinkel
Debbie M
DM
The Princess Margaret Hospital and the Ontario Cancer Institute, Rm 9-516, 610 University Ave, M5G 2M9, Toronto, ON, Canada.
Chow
Sue
S
Hurren
Rose
R
Gronda
Marcela
M
Henderson
Clare
C
Berube
Christina
C
Hedley
David W
DW
Schimmer
Aaron D
AD
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D053143:Caspase 2 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D004721:Endoplasmic Reticulum / Q000187:drug effects*; D006801:Humans; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008954:Models, Biological; D053978:Pentacyclic Triterpenes; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C017032:asiatic acid; D053143:Caspase 2; D053148:Caspase 3; D020169:Caspases; D002118:Calcium