The effects of taurolidine alone and in combination with doxorubicin or carboplatin in canine osteosarcoma in vitro

Taurolidine was cytotoxic to osteosarcoma cells and increased the toxicity of doxorubicin and carboplatin in vitro. Apoptosis was greatly induced in cells exposed to 125 μM taurolidine and less so in cells exposed to 250 μM taurolidine. Taurolidine cytotoxicity appeared caspase-dependent in one cell line; with apparent mutant p53 protein. This cell line was the most sensitive to single agent taurolidine treatment and had a taurolidine-dependent reduction in accumulated p53 protein suggesting taurolidine’s effects may depend on the functional status of p53 in canine OS.Taurolidine’s cytotoxic effect appears dependent on cell specific factors which may be explained, in part, by the functional status of p53. Taurolidine initiates apoptosis in canine OS cells and this occurs to a greater extent at lower concentrations. Mechanisms of cell death induced by higher concentrations were not elucidated here. Taurolidine combined with doxorubicin or carboplatin can increase the toxicity of these chemotherapy drugs and warrants further investigation in dogs with osteosarcoma.Osteosarcoma (OS) is the most common cancer of bone in dogs [1]. Tumors usually arise in the appendicular skeleton and metastasize to the lung. In cases with localized appendicular disease, amputation of the affected limb along with chemotherapy can extend life expectancy up to about 12 months on average but there is no cure. An increased understanding of the pathogenesis of OS is needed in order to facilitate the development of more effective therapeutic strategies. One such strategy is to combine drugs with different mechanisms of action in an attempt to overcome tumor heterogeneity and drug resistance. In this regard, it is reasonable to consider adding new antineoplastic drugs to the treatments of patients receiving traditional chemotherapeutics and one such candidate for this is the antimicrobial and antineoplastic drug taurolidine [2,3].Taurolidine is a derivative of the amino acid taurine that has ant