Search

Your search keyword '"PROTEINE BCL-2"' showing total 2 results
Start Over Descriptor "PROTEINE BCL-2" Search Limiters Full Text
2 results on '"PROTEINE BCL-2"'

1. Résistance au cisplatin dans le cancer ovarien : rôle de la protéine anti-apoptotique Bcl-2?

Author

Bélanger, Sylvie, Piché, Alain, Bélanger, Sylvie, and Piché, Alain

Abstract

Plusieurs évidences suggèrent que des membres impliqués dans le contrôle de l'activation de la cascade apoptotique et particulièrement les membres de la famille de protéines Bcl-2 pourraient jouer un rôle dans le phénomène de résistance observé dans les tumeurs ovariennes. Le but de cette étude est de déterminer l'importance relative de la protéine Bcl-2 dans le phénomène de résistance clinique à la chimiothérapie dans le cancer ovarien, plus précisément au cisplatin. L'analyse de l'expression de la protéine Bcl-2 dans des cellules d'ovaire normales et cancéreuses a démontré une surexpression de la protéine dans les cellules cancéreuses par rapport aux cellules d'ovaire normales, mais aucune corrélation entre l'expression de la protéine Bcl-2 et la sensibilité au cisplatin des cellules d'ovaire cancéreuses n'a pu être établie. Pour pouvoir mieux évaluer le rôle de la protéine Bcl-2 dans le phénomène de résistance, nous avons utilisé un anticorps monovalent modifié (scFv) dirigé contre cette dernière. Ce scFv agit essentiellement comme un inhibiteur spécifique de la protéine Bcl-2 ans les cellules.

Published
2003

2. Use of Human Cancer Cell Lines Mitochondria to Explore the Mechanisms of BH3 Peptides and ABT-737-Induced Mitochondrial Membrane Permeabilization

Author

Pierre Rustin, Christine Péchoux, Magali Brabant, Diana Desgué, Etienne Jacotot, Nelly Buron, Myriam Lassalle, Mathieu Porceddu, Annie Borgne-Sanchez, Cindy Racoeur, Theraptosis S.A., Mitologics SAS, Hôpital Robert Debré, Unité de recherche génomique et physiologie de la lactation (GPL), Institut National de la Recherche Agronomique (INRA), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Department of Reproductive Biology, and Imperial College London

Subjects
Non-Clinical Medicine/Research Methods, [SDV]Life Sciences [q-bio], Mitochondrion, Mitochondrial apoptosis-induced channel, Piperazines, Membrane Potentials, Nitrophenols, Mice, 0302 clinical medicine, BIOLOGIE CELLULAIRE, Inner mitochondrial membrane, Mice, Inbred BALB C, Sulfonamides, 0303 health sciences, Multidisciplinary, biology, Cytochrome c, Cell Biology/Cellular Death and Stress Responses, CANCER, Mitochondria, 3. Good health, Cell biology, PROTEINE BCL-2, Gene Expression Regulation, Neoplastic, Cross-Linking Reagents, Proto-Oncogene Proteins c-bcl-2, Biochemistry, mitochondrie, protéine, 030220 oncology & carcinogenesis, Mitochondrial Membranes, Medicine, Female, Biotechnology/Protein Chemistry and Proteomics, Biochemistry/Drug Discovery, biological phenomena, cell phenomena, and immunity, Bacterial outer membrane, Research Article, Science, Oncology/Oncology Agents, Permeability, 03 medical and health sciences, Cell Line, Tumor, Proto-Oncogene Proteins, Animals, Humans, [INFO]Computer Science [cs], 030304 developmental biology, apoptose, Biphenyl Compounds, Peptide Fragments, CYTOCHROME-C RELEASE, BCL-2 FAMILY PROTEINS, MIMETIC ABT-737, OUTER-MEMBRANE, CASPASE ACTIVATION, BAX, APOPTOSIS, DEATH, INHIBITORS, DOMAINS, membrane cellulaire, Apoptosis, Cancer cell, biology.protein, Apoptosome, humain
Abstract

International audience; Current limitations of chemotherapy include toxicity on healthy tissues and multidrug resistance of malignant cells. A number of recent anti-cancer strategies aim at targeting the mitochondrial apoptotic machinery to induce tumor cell death. In this study, we set up protocols to purify functional mitochondria from various human cell lines to analyze the effect of peptidic and xenobiotic compounds described to harbour either Bcl-2 inhibition properties or toxic effects related to mitochondria. Mitochondrial inner and outer membrane permeabilization were systematically investigated in cancer cell mitochondria versus non-cancerous mitochondria. The truncated (t-) Bid protein, synthetic BH3 peptides from Bim and Bak, and the small molecule ABT-737 induced a tumor-specific and OMP-restricted mitochondrio-toxicity, while compounds like HA-14.1, YC-137, Chelerythrine, Gossypol, TW-37 or EM20-25 did not. We found that ABT-737 can induce the Bax-dependent release of apoptotic proteins (cytochrome c, Smac/Diablo and Omi/HtrA2 but not AIF) from various but not all cancer cell mitochondria. Furthermore, ABT-737 addition to isolated cancer cell mitochondria induced oligomerization of Bax and/or Bak monomers already inserted in the mitochondrial membrane. Finally immunoprecipatations indicated that ABT-737 induces Bax, Bak and Bim desequestration from Bcl-2 and Bcl-xL but not from Mcl-1L. This study investigates for the first time the mechanism of action of ABT-737 as a single agent on isolated cancer cell mitochondria. Hence, this method based on MOMP (mitochondrial outer membrane permeabilization) is an interesting screening tool, tailored for identifying Bcl-2 antagonists with selective toxicity profile against cancer cell mitochondria but devoid of toxicity against healthy mitochondria.

Published
2010

Catalog

Books, media, physical & digital resources
See catalog results