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Open Access Highly Accessed Research article

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

Kevin Marley1, Stuart C Helfand1, Wade A Edris14, John E Mata2, Alix I Gitelman3, Jan Medlock2 and Bernard Séguin15*

Author affiliations

1 Department of Clinical Sciences, Oregon State University, Corvallis, USA

2 Department of Biomedical Sciences, Oregon State University, Corvallis, USA

3 Department of Statistics, Oregon State University, Corvallis, Oregon 97331, USA

4 Present address: Department of Cellular and Molecular Physiology, Milton S Hershey Medical Center Penn State University, 500 University Dr. Hershey, Pennsylvania 17033, USA

5 Department of Clinical Sciences, Colorado State University, Fort Collins, Colorado 80523, USA

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Citation and License

BMC Veterinary Research 2013, 9:15  doi:10.1186/1746-6148-9-15

Published: 18 January 2013

Abstract

Background

Osteosarcoma (OS) affects over 8000 dogs/year in the United States. The disease usually arises in the appendicular skeleton and metastasizes to the lung. Dogs with localized appendicular disease benefit from limb amputation and chemotherapy but most die within 6–12 months despite these treatments. Taurolidine, a derivative of taurine, has anti-tumor and anti-angiogenic effects against a variety of cancers. The following in vitro studies tested taurolidine as a candidate for adjuvant therapy for canine OS. Tests for p53 protein status and caspase activity were used to elucidate mechanisms of taurolidine-induced cell death.

Results

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.

Conclusion

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.

Keywords:
Taurolidine; Osteosarcoma; In vitro; Apoptosis; Doxorubicin; Carboplatin