Boswellic acids and malignant glioma: induction of apoptosis but no modulation of drug sensitivity
| Autor: | M. Schabet, Hasan Safayhi, Stephan Winter, Hermann P. T. Ammon, E.-R. Sailer, Peter Groscurth, Michael Weller, Tamara Glaser |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Cancer Research pentacyclic triterpenes Fas Ligand Protein medicine.medical_treatment Cell Apoptosis Biology chemotherapy Mice chemistry.chemical_compound Bcl-2-associated X protein Cyclins Proto-Oncogene Proteins Glioma Tumor Cells Cultured medicine Animals Humans brain tumour Cytotoxicity bcl-2-Associated X Protein Membrane Glycoproteins Regular Article Drug Synergism Fas receptor medicine.disease Antineoplastic Agents Phytogenic Triterpenes Neoplasm Proteins Cytokine medicine.anatomical_structure Proto-Oncogene Proteins c-bcl-2 Oncology chemistry Biochemistry glioma cells Drug Resistance Neoplasm Cancer research biology.protein Boswellic acid Tumor Suppressor Protein p53 Reactive Oxygen Species |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/sj.bjc.6690419 |
| Popis: | Steroids are essential for the control of oedema in human malignant glioma patients but may interfere with the efficacy of chemotherapy. Boswellic acids are phytotherapeutic anti-inflammatory agents that may be alternative drugs to corticosteroids in the treatment of cerebral oedema. Here, we report that boswellic acids are cytotoxic to malignant glioma cells at low micromolar concentrations. In-situ DNA end labelling and electron microscopy reveal that boswellic acids induce apoptosis. Boswellic acid-induced apoptosis requires protein, but not RNA synthesis, and is neither associated with free radical formation nor blocked by free radical scavengers. The levels of BAX and BCL-2 proteins remain unaltered during boswellic acid-induced apoptosis. p21 expression is induced by boswellic acids via a p53-independent pathway. Ectopic expression of wild-type p53 also induces p21, and facilitates boswellic acid-induced apoptosis. However, targeted disruption of the p21 genes in colon carcinoma cells enhances rather than decreases boswellic acid toxicity. Ectopic expression of neither BCL-2 nor the caspase inhibitor, CRM-A, is protective. In contrast to steroids, subtoxic concentrations of boswellic acids do not interfere with cancer drug toxicity of glioma cells in acute cytotoxicity or clonogenic cell death assays. Also, in contrast to steroids, boswellic acids synergize with the cytotoxic cytokine, CD95 ligand, in inducing glioma cell apoptosis. This effect is probably mediated by inhibition of RNA synthesis and is not associated with changes of CD95 expression at the cell surface. Further studies in laboratory animals and in human patients are required to determine whether boswellic acids may be a useful adjunct to the medical management of human malignant glioma. © 1999 Cancer Research Campaign |
| Databáze: | OpenAIRE |
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