lu-28-179 and Fibrosarcoma

lu-28-179 has been researched along with Fibrosarcoma* in 1 studies

Other Studies

1 other study(ies) available for lu-28-179 and Fibrosarcoma

ArticleYear
Effective tumor cell death by sigma-2 receptor ligand siramesine involves lysosomal leakage and oxidative stress.
    Cancer research, 2005, Oct-01, Volume: 65, Issue:19

    Acquired resistance to classic caspase-mediated apoptosis is a common problem for the treatment of human cancer. Here, we show that siramesine, a novel sigma-2 receptor ligand, effectively induces caspase-independent programmed cell death in immortalized and transformed cells of various origins. Siramesine-treated tumor cells displayed increased levels of reactive oxygen species, lysosomal membrane permeabilization, chromatin condensation, and shrinkage and detachment of cells. Lipid antioxidants (alpha-tocopherol and gamma-tocopherol), but not other tested antioxidants (butylated hydroxyanisol or N-acetyl cysteine), effectively inhibited siramesine-induced morphologic changes and cell death. Cathepsin B inhibitors (CA-074-Me and R-2525) conferred similar, but less pronounced protection, whereas ectopic expression of antiapoptotic protein Bcl-2, lack of wild-type p53 as well as pharmacologic inhibitors of caspases (zVAD-fmk, DEVD-CHO, and LEHD-CHO), calpains (PD150606), and serine proteases (N-tosyl-L-phenylalanine chloromethyl ketone and pefabloc) failed to protect cells against siramesine-induced death. Importantly, transformation of murine embryonic fibroblasts with activated c-src or v-Ha-ras oncogenes greatly sensitized them to siramesine-induced cytotoxicity. Furthermore, p.o. administration of well-tolerated doses of siramesine had a significant antitumorigenic effect in orthotopic breast cancer and s.c. fibrosarcoma models in mice. These results present siramesine as a promising new drug for the treatment of tumors resistant to traditional therapies.

    Topics: Animals; Antineoplastic Agents; Apoptosis; Breast Neoplasms; Caspases; Cathepsins; Cell Line, Transformed; Cell Line, Tumor; Cytochromes c; Female; Fibrosarcoma; Humans; Indoles; Ligands; Lysosomes; Mice; Mice, Inbred BALB C; NIH 3T3 Cells; Oxidative Stress; Receptors, sigma; Spiro Compounds; Tumor Suppressor Protein p53; Xenograft Model Antitumor Assays

2005