Assessment of the antiinvasive potential of the anthracycline aclacinomycin (Aclarubicin) in a human fibrosarcoma cell line. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue International Journal of Oncology Année : 2004

Assessment of the antiinvasive potential of the anthracycline aclacinomycin (Aclarubicin) in a human fibrosarcoma cell line.

Résumé

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.
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Dates et versions

inserm-00147796 , version 1 (21-05-2007)

Identifiants

  • HAL Id : inserm-00147796 , version 1
  • PUBMED : 15138606

Citer

Salima Addadi-Rebbah, Stephane Poitevin, Nicolas Fourre, Myriam C. Polette, Roselyne Garnotel, et al.. Assessment of the antiinvasive potential of the anthracycline aclacinomycin (Aclarubicin) in a human fibrosarcoma cell line.. International Journal of Oncology, 2004, 24 (6), pp.1607-15. ⟨inserm-00147796⟩

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