Assessment of the antiinvasive potential of the anthracycline aclacinomycin (Aclarubicin) in a human fibrosarcoma cell line
| Autor: | Addadi-Rebbah, S., Poitevin, S., Fourre, N., Myriam POLETTE, Garnotel, R., Jeannesson, P. |
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| Přispěvatelé: | Birembaut, Philippe, Médicaments : Dynamique Intracellulaire et Architecture Nucléaire (MéDIAN), Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Dynamique cellulaire et moléculaire de la muqueuse respiratoire, Université de Reims Champagne-Ardenne (URCA)-IFR53-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Předmět: |
Integrins
Fibrosarcoma [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract MESH: Cell Adhesion CSK Tyrosine-Protein Kinase Cell Movement Cell Adhesion Tumor Cells Cultured Humans Neoplasm Invasiveness MESH: Antibiotics Antineoplastic Aclarubicin MESH: Cell Movement MESH: Focal Adhesion Protein-Tyrosine Kinases MESH: Humans Antibiotics Antineoplastic MESH: Culture Media Conditioned MESH: Fibrosarcoma MESH: Aclarubicin MESH: Matrix Metalloproteinase 9 MESH: Integrins Protein-Tyrosine Kinases MESH: Matrix Metalloproteinase 2 src-Family Kinases Matrix Metalloproteinase 9 Culture Media Conditioned Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Matrix Metalloproteinase 2 [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract MESH: Focal Adhesion Kinase 1 |
| Zdroj: | Scopus-Elsevier International Journal of Oncology International Journal of Oncology, 2004, 24 (6), pp.1607-15 International Journal of Oncology, Spandidos Publications, 2004, 24 (6), pp.1607-15 |
| ISSN: | 1019-6439 1791-2423 |
| Popis: | Aclacinomycin (Aclarubicin) is a trisaccharide anthracycline anticancer drug active against a wide variety of solid tumors and haematological malignancies. We have evaluated its antimigrative and antiinvasive properties in a Boyden chamber with or without Matrigel and in wound repair assays. Aclacinomycin was demonstrated to inhibit HT-1080 cell migration and invasion while being more potent than the classical anthracycline doxorubicin. This decrease occurred in a dose-dependent manner and without affecting cell proliferation. Importantly, the antiinvasive effect was not associated to a modification in the production of the matrix-degrading enzymes MMP-2 and MMP-9 but rather to changes in cytoskeletal and focal contact formation. Indeed, the drug reduces cell polarity, impairs the actin-mediated membrane ruffling at the leading edge and decreases beta1 integrin expression and activation. Dramatic alterations in the distribution of vinculin and in the expression and phosphorylation state of both FAK and Src kinases were also detected. As a conclusion, these data suggest a novel application for this chemotherapeutic agent due to its ability to reduce tumor cell invasion. Combination of aclacinomycin with MMP inhibitors could have therapeutic potential in preventing tumor metastasis. |
| Databáze: | OpenAIRE |
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