Betulinic acid-induced apoptosis in glioma cells: A sequential requirement for new protein synthesis, formation of reactive oxygen species, and caspase processing. Wick, W, Grimmel, C, Wagenknecht, B, Dichgans, J, & Weller, M The Journal of Pharmacology and Experimental Therapeutics, 289(3):1306–1312, June, 1999. ![Betulinic acid-induced apoptosis in glioma cells: A sequential requirement for new protein synthesis, formation of reactive oxygen species, and caspase processing [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper abstract bibtex Betulinic acid (BA), a pentacyclic triterpene, is an experimental cytotoxic agent for malignant melanoma. Here, we show that BA triggers apoptosis in five human glioma cell lines. BA-induced apoptosis requires new protein, but not RNA, synthesis, is independent of p53, and results in p21 protein accumulation in the absence of a cell cycle arrest. BA-induced apoptosis involves the activation of caspases that cleave poly(ADP ribose)polymerase. Interactions of death ligand/receptor pairs of the CD95/CD95 ligand family do not mediate BA-induced caspase activation. BA enhances the levels of BAX and BCL-2 proteins but does not alter the levels of BCL-xS or BCL-xL. Ectopic expression of BCL-2 prevents BA-induced caspase activation, DNA fragmentation, and cell death. Furthermore, BA induces the formation of reactive oxygen species that are essential for BA-triggered cell death. The generation of reactive oxygen species is blocked by BCL-2 and requires new protein synthesis but is unaffected by caspase inhibitors, suggesting that BA toxicity sequentially involves new protein synthesis, formation of reactive oxygen species, and activation of crm-A-insensitive caspases.
@article{wick_betulinic_1999,
title = {Betulinic acid-induced apoptosis in glioma cells: {A} sequential requirement for new protein synthesis, formation of reactive oxygen species, and caspase processing},
volume = {289},
issn = {0022-3565},
shorttitle = {Betulinic acid-induced apoptosis in glioma cells},
url = {http://www.ncbi.nlm.nih.gov/pubmed/10336521},
abstract = {Betulinic acid (BA), a pentacyclic triterpene, is an experimental cytotoxic agent for malignant melanoma. Here, we show that BA triggers apoptosis in five human glioma cell lines. BA-induced apoptosis requires new protein, but not RNA, synthesis, is independent of p53, and results in p21 protein accumulation in the absence of a cell cycle arrest. BA-induced apoptosis involves the activation of caspases that cleave poly(ADP ribose)polymerase. Interactions of death ligand/receptor pairs of the CD95/CD95 ligand family do not mediate BA-induced caspase activation. BA enhances the levels of BAX and BCL-2 proteins but does not alter the levels of BCL-xS or BCL-xL. Ectopic expression of BCL-2 prevents BA-induced caspase activation, DNA fragmentation, and cell death. Furthermore, BA induces the formation of reactive oxygen species that are essential for BA-triggered cell death. The generation of reactive oxygen species is blocked by BCL-2 and requires new protein synthesis but is unaffected by caspase inhibitors, suggesting that BA toxicity sequentially involves new protein synthesis, formation of reactive oxygen species, and activation of crm-A-insensitive caspases.},
number = {3},
urldate = {2012-01-03},
journal = {The Journal of Pharmacology and Experimental Therapeutics},
author = {Wick, W and Grimmel, C and Wagenknecht, B and Dichgans, J and Weller, M},
month = jun,
year = {1999},
pmid = {10336521},
keywords = {Antigens, CD95, Antineoplastic Agents, Phytogenic, Apoptosis, Caspases, Cell Cycle, Cell Division, Cell Survival, Cyclin-Dependent Kinase Inhibitor p21, Cyclins, Cycloheximide, Cysteine Proteinase Inhibitors, DNA Fragmentation, Enzyme Activation, Fas Ligand Protein, Glioma, Humans, Kinetics, Membrane Glycoproteins, Oligopeptides, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, Reactive Oxygen Species, Triterpenes, Tumor Cells, Cultured, bcl-2-Associated X Protein, bcl-X Protein},
pages = {1306--1312},
}
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BA-induced apoptosis requires new protein, but not RNA, synthesis, is independent of p53, and results in p21 protein accumulation in the absence of a cell cycle arrest. BA-induced apoptosis involves the activation of caspases that cleave poly(ADP ribose)polymerase. Interactions of death ligand/receptor pairs of the CD95/CD95 ligand family do not mediate BA-induced caspase activation. BA enhances the levels of BAX and BCL-2 proteins but does not alter the levels of BCL-xS or BCL-xL. Ectopic expression of BCL-2 prevents BA-induced caspase activation, DNA fragmentation, and cell death. Furthermore, BA induces the formation of reactive oxygen species that are essential for BA-triggered cell death. 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