Bulbispermine: A Crinine-Type Amaryllidaceae Alkaloid Exhibiting Cytostatic Activity toward Apoptosis-Resistant Glioma Cells
| Autor: | Alexander Kornienko, Snezna Rogelj, Anna Andolfi, Stephen C. Pelly, Véronique Mathieu, Robert Kiss, Robert Johnston, Willem A. L. van Otterlo, Igor V. Magedov, Florence Lefranc, Delphine Lamoral-Theys, Mary R. Reisenauer, Kathryn Hayden, Cody Champion, Giovanni Luchetti, Antonio Evidente |
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| Přispěvatelé: | G., Luchetti, R., Johnston, V., Mathieu, F., Lefranc, K., Hayden, Andolfi, Anna, D., Lamoral They, M. R., Reisenauer, C., Champion, S. C., Pelly, W. A., L., I. V., Magedov, R., Ki, Evidente, Antonio, S., Rogelj, A., Kornienko |
| Rok vydání: | 2012 |
| Předmět: |
Cell type
ANTINEOPLASTIC AGENTS Pharmacology Biology CYTOTOXIC ACTIVITY Plant Roots Biochemistry Article Inhibitory Concentration 50 Glioma Drug Discovery medicine Humans Computer Simulation BIOLOGICAL EVALUATION CANCER-CELLS General Pharmacology Toxicology and Pharmaceutics Amaryllidaceae Alkaloids IN-VIVO Molecular Structure GLIOBLASTOMA CELLS LYCORINE ALKALOIDS Alkaloid Organic Chemistry ACTIN CYTOSKELETON Cancer Actin cytoskeleton medicine.disease Antineoplastic Agents Phytogenic In vitro Drug Resistance Neoplasm Apoptosis Molecular Medicine BULBS Drug Screening Assays Antitumor PANCRATISTATIN |
| Zdroj: | ChemMedChem. 7:815-822 |
| ISSN: | 1860-7179 |
| Popis: | The Amaryllidaceae alkaloid bulbispermine was derivatized to produce a small group of synthetic analogues. These, together with bulbispermine's natural crinine-type congeners, were evaluated in vitro against a panel of cancer cell lines with various levels of resistance to pro-apoptotic stimuli. Bulbispermine, haemanthamine, and haemanthidine showed the most potent antiproliferative activities as determined by the MTT colorimetric assay. Among the synthetic bulbispermine analogues, only the C1,C2-dicarbamate derivative exhibited notable growth inhibitory properties. All active compounds were found not to discriminate between the cancer cell lines based on the apoptosis sensitivity criterion; they displayed similar potencies in both cell types, indicating that the induction of apoptosis is not the primary mechanism responsible for antiproliferative activity in this series of compounds. It was also found that bulbispermine inhibits the proliferation of glioblastoma cells through cytostatic effects, possibly arising from rigidification of the actin cytoskeleton. These findings lead us to argue that crinine-type alkaloids are potentially useful drug leads for the treatment of apoptosis-resistant cancers and glioblastoma in particular. |
| Databáze: | OpenAIRE |
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