Amitozyn impairs chromosome segregation and induces apoptosis via mitotic checkpoint activation
| Autor: | Bastien Herman, Sergey Tcherniuk, Jadwiga Chroboczek, Anatoly I. Potopalsky, Aldrian Gudrun |
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| Přispěvatelé: | TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF) |
| Rok vydání: | 2012 |
| Předmět: |
Phytochemistry
[SDV]Life Sciences [q-bio] Phytopharmacology Phytochemicals Cancer Treatment lcsh:Medicine Apoptosis Toxicology Biochemistry Retinoblastoma Protein HeLa 0302 clinical medicine Tubulin Chromosome Segregation Molecular Cell Biology DNA Breaks Double-Stranded lcsh:Science 0303 health sciences Multidisciplinary Cell Death Clinical Pharmacology Applied Chemistry Retinoblastoma protein 3. Good health Cell biology Chemistry Phenotype Oncology 030220 oncology & carcinogenesis Medicine Cell Division Research Article Signal Transduction Drugs and Devices Drug Research and Development Mitotic index Toxic Agents Biology 03 medical and health sciences Cell Line Tumor Chemical Biology Humans Mitosis 030304 developmental biology Cell Proliferation Benzophenanthridines Cell growth lcsh:R Correction Organothiophosphorus Compounds biology.organism_classification Molecular biology Antineoplastic Agents Phytogenic Small Molecules Cell culture Ethnopharmacology biology.protein M Phase Cell Cycle Checkpoints lcsh:Q Medicinal Chemistry Protein Multimerization HeLa Cells |
| Zdroj: | PLoS ONE PLoS ONE, 2013, 8 (3), pp.e57461. ⟨10.1371/journal.pone.0057461⟩ PLoS ONE, Public Library of Science, 2013, 8 (3), pp.e57461. ⟨10.1371/journal.pone.0057461⟩ PLoS ONE, Vol 8, Iss 3, p e57461 (2013) |
| ISSN: | 1932-6203 |
| Popis: | International audience; Amitozyn (Am) is a semi-synthetic drug produced by the alkylation of major celandine (Chelidonium majus L.) alkaloids with the organophosphorous compound N,N'N'-triethylenethiophosphoramide (ThioTEPA). We show here that the treatment of living cells with Am reversibly perturbs the microtubule cytoskeleton, provoking a dose-dependent cell arrest in the M phase. Am changed the dynamics of tubulin polymerization in vitro, promoted the appearance of aberrant mitotic phenotypes in HeLa cells and induced apoptosis by the activation of caspase-9, caspase-3 and PARP, without inducing DNA breaks. Am treatment of HeLa cells induced changes in the phosphorylation of the growth suppressor pRb that coincided with maximum mitotic index. The dose-dependent and reversible anti-proliferative effect of Am was observed in several transformed cell lines. Importantly, the drug was also efficient against multidrug-resistant, paclitaxel-resistant or p53-deficient cells. Our results thus open the way to further pre-clinical evaluation of Am. |
| Databáze: | OpenAIRE |
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