Disruption of the endoplasmic reticulum and increases in cytoplasmic calcium are early events in cell death induced by the natural triterpenoid Asiatic acid
| Autor: | Clare Henderson, Debbie M. Gurfinkel, David W. Hedley, Christina Berube, Aaron D. Schimmer, Rose Hurren, Marcela Gronda, Sue Chow |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Cancer Research Programmed cell death medicine.medical_specialty Cytoplasm Cell Survival Clinical Biochemistry Caspase 2 Pharmaceutical Science chemistry.chemical_element Calcium Endoplasmic Reticulum Models Biological Lethal Dose 50 Mice Internal medicine medicine Tumor Cells Cultured Animals Humans Caspase Pharmacology Calcium metabolism biology Cell Death Caspase 3 Endoplasmic reticulum Biochemistry (medical) Prostatic Neoplasms Cell Biology Triterpenes Cell biology Endocrinology Mechanism of action chemistry Apoptosis Drug Resistance Neoplasm Caspases biology.protein medicine.symptom Pentacyclic Triterpenes |
| Zdroj: | Apoptosis : an international journal on programmed cell death. 11(9) |
| ISSN: | 1360-8185 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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