aclarubicin and Fibrosarcoma

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.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Cell Adhesion; Cell Movement; CSK Tyrosine-Protein Kinase; Culture Media, Conditioned; Fibrosarcoma; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Humans; Integrins; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Neoplasm Invasiveness; Protein-Tyrosine Kinases; src-Family Kinases; Tumor Cells, Cultured

After the intraperitoneal injection of aclacinomycin into mice, a variety of immune responses were increased. The total plaque-forming spleen cell response to SRBC was higher in treated animals than in controls, in spite of an apparent cytotoxic effects on B cells. The aclacinomycin-sensitive cell is apparently a long-lived cell, surviving adult thymectomy. Delayed-type hypersensitivity reactions were also augmented in treated animals, particularly those bearing tumors. In adjuvant-treated mice, the injection of aclacinomycin augments the immune response still further. Such observations should be taken into account in the establishment of clinical protocols associating immunotherapy and chemotherapy.

Topics: Aclarubicin; Adjuvants, Immunologic; Animals; Antibody Formation; Antibody-Producing Cells; BCG Vaccine; Fibrosarcoma; Hemolytic Plaque Technique; Hypersensitivity, Delayed; Immunity, Cellular; Injections, Intraperitoneal; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Naphthacenes; Sheep