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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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Abstract

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.

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Authors and Affiliations

  1. The Princess Margaret Hospital and the Ontario Cancer Institute, Rm 9-516, 610 University Ave, M5G 2M9, Toronto, ON, Canada

    Debbie M. Gurfinkel, Sue Chow, Rose Hurren, Marcela Gronda, Clare Henderson, Christina Berube, David W. Hedley & Aaron D. Schimmer

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  1. Debbie M. Gurfinkel
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  2. Sue Chow
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  3. Rose Hurren
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  4. Marcela Gronda
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  5. Clare Henderson
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  6. Christina Berube
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  7. David W. Hedley
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  8. Aaron D. Schimmer
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Correspondence to Aaron D. Schimmer.

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Gurfinkel, D.M., Chow, S., Hurren, R. et al. Disruption of the endoplasmic reticulum and increases in cytoplasmic calcium are early events in cell death induced by the natural triterpenoid Asiatic acid. Apoptosis 11, 1463–1471 (2006). https://doi.org/10.1007/s10495-006-9086-z

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  • DOI: https://doi.org/10.1007/s10495-006-9086-z

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