Peptide screen identifies a new NADPH oxidase inhibitor: impact on cell migration and invasion
| Autor: | Françoise Garrouste, Mohamed Mousslim, Sylvia Pietri, Vincent Peyrot, Sophie Thétiot-Laurent, Sylvie Thuault, Alessandra Pagano, Jean-Marc Sabatier, Nicolas Andreotti, Marcel Culcasi, Hervé Kovacic, Fabrice Parat, José Luis |
|---|---|
| Přispěvatelé: | Gènes HLA-DR, Autoanticorps et Microchimérisme dans la Polyarthrite Rhumatoïde et la Sclérodermie (HLA-DR), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie Radicalaire (ICR), Aix Marseille Université (AMU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU) |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Peptide 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Movement Cell Line Tumor [CHIM]Chemical Sciences Humans Neoplasm Invasiveness Amino Acid Sequence Enzyme Inhibitors Xanthine oxidase ComputingMilieux_MISCELLANEOUS Cell Proliferation Pharmacology chemistry.chemical_classification Reactive oxygen species NADPH oxidase biology Superoxide NADPH Oxidases Cell migration Molecular biology 030104 developmental biology Enzyme Biochemistry chemistry 030220 oncology & carcinogenesis NOX1 cardiovascular system biology.protein NADPH Oxidase 1 Drug Screening Assays Antitumor Oligopeptides |
| Zdroj: | European Journal of Pharmacology European Journal of Pharmacology, 2016, ⟨10.1016/j.ejphar.2016.10.011⟩ |
| ISSN: | 1879-0712 |
| DOI: | 10.1016/j.ejphar.2016.10.011⟩ |
| Popis: | The NADPH oxidase proteins catalyse the formation of superoxide anion which act as signalling molecules in physiological and pathological processes. Nox1-dependent NADPH oxidase is expressed in heart, lung, colon, blood vessels and brain. Different strategies involving Nox1 inhibition based on diphenylene iodonium derivatives are currently tested for colorectal cancer therapy. Here, after peptides screening on Nox1-dependent NADPH oxidase assay in HT-29 cells, we identify a peptide (referred to as NF02), cell-active, that potently block Nox1-dependent reactive oxygen species generation. Study of DEPMPO adduct formation by electron paramagnetic resonance showed that NF02 has no superoxide scavenging activity and no impact on cellular reactive oxygen species-producing enzymes such xanthine oxidase. NF02 was not cytotoxic, inhibited reactive oxygen species production of reconstituted Nox1/Noxo1/Noxa1 complex in HEK293 and did not decrease Nox2 dependent cellular NADPH oxidase reactive oxygen species production. Finally, NF02 inhibited cell migration and invasion of colorectal cancer cells which is consistent with the described impact of Nox1 inhibitors on cell migration. NF02 peptide is a new NADPH oxidase inhibitor specific for Nox1 over Nox2 and xanthine oxidase which might represent a useful Nox1 tool with potential therapeutic insights. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect