A novel synthetic inhibitor of CDC25 phosphatases: BN82002
| Autor: | Marie-Christine, Brezak, Muriel, Quaranta, Odile, Mondésert, Marie-Odile, Galcera, Olivier, Lavergne, Frédéric, Alby, Martine, Cazales, Véronique, Baldin, Christophe, Thurieau, Jeremiath, Harnett, Christophe, Lanco, Philip G, Kasprzyk, Gregoire P, Prevost, Bernard, Ducommun |
|---|---|
| Přispěvatelé: | Institut Henri Beaufour (IPSEN), IPSEN-BEAUFOUR, Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Biomeasure, Milford |
| Rok vydání: | 2004 |
| Předmět: |
MESH: Xenograft Model Antitumor Assays
MESH: Cell Line Tumor Mice Nude Mitosis MESH: Cell Cycle Antineoplastic Agents Cell Cycle Proteins [SDV.BC]Life Sciences [q-bio]/Cellular Biology MESH: Ethylamines Mice MESH: Cell Cycle Proteins MESH: cdc25 Phosphatases Cell Line Tumor MESH: Mice Nude Ethylamines Animals Humans cdc25 Phosphatases MESH: Animals Enzyme Inhibitors MESH: Mice MESH: Humans MESH: Drug Screening Assays Antitumor Cell Cycle MESH: Mitosis Nitro Compounds Xenograft Model Antitumor Assays MESH: Nitro Compounds MESH: Hela Cells Pancreatic Neoplasms enzymes and coenzymes (carbohydrates) MESH: Enzyme Inhibitors MESH: Antineoplastic Agents MESH: Cell Division Female MESH: Pancreatic Neoplasms biological phenomena cell phenomena and immunity Drug Screening Assays Antitumor MESH: Female Cell Division HeLa Cells |
| Zdroj: | Cancer Research Cancer Research, American Association for Cancer Research, 2004, 64 (9), pp.3320-5 |
| ISSN: | 0008-5472 1538-7445 |
| Popis: | CDC25 dual-specificity phosphatases are essential regulators that dephosphorylate and activate cyclin-dependent kinase/cyclin complexes at key transitions of the cell cycle. CDC25 activity is currently considered to be an interesting target for the development of new antiproliferative agents. Here we report the identification of a new CDC25 inhibitor and the characterization of its effects at the molecular and cellular levels, and in animal models. BN82002 inhibits the phosphatase activity of recombinant human CDC25A, B, and C in vitro. It impairs the proliferation of tumoral cell lines and increases cyclin-dependent kinase 1 inhibitory tyrosine phosphorylation. In synchronized HeLa cells, BN82002 delays cell cycle progression at G1-S, in S phase and at the G2-M transition. In contrast, BN82002 arrests U2OS cell cycle mostly in the G1 phase. Selectivity of this inhibitor is demonstrated: (a) by the reversion of the mitotic-inducing effect observed in HeLa cells upon CDC25B overexpression; and (b) by the partial reversion of cell cycle arrest in U2OS expressing CDC25. We also show that BN82002 reduces growth rate of human tumor xenografts in athymic nude mice. BN82002 is a original CDC25 inhibitor that is active both in cell and animal models. This greatly reinforces the interest in CDC25 as an anticancer target. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|