Investigation of sodium dichloroacetate (DCA) for the treatment of canine neoplasms: in vitro and in vivo preclinical assays

Abstract

Nowadays, cancer represents a major challenge for science and medical practice in man. As for the animals, the problem is not different: it is necessary to intensify research in Veterinary Oncology in all its aspects, particularly with regard to new treatments for cancers in animals. The efficiency of an anticancer agent for the treatment of a particular cancer can only be definitely determined by clinical trials. However, due to ethical reasons, studies have to start in experimental systems. This project aims to investigate the sodium dichloroacetate as a possible new cancer therapy for canine tumors, performing in vitro and in vivo preclinical assays. The DCA, dichloroacetic acid is an analogue of acetic acid in which two of the three hydrogen atoms of the methyl group have been replaced by chlorine atoms. The salt of dichloroacetic acid and esters are called dichloroacetate. The sodium dichloroacetate is under investigation as a possible treatment for cancer. In this project, the sodium dichloroacetate will be tested in primary cultures of canine neoplastic cells. Neoplastic cells derived from spontaneous canine tumors ( breast, bone, mast cell tumors, melanomas and hemangiosarcoma) dogs will be harvested and cultured. Treatment with DCA will follow in doses reported in the literature (0.5 mM, 1 mM, 2 mM, 5 mM and 10 mM) for 7 days. Both cell proliferation as cell death will be quantified. If in vitro positive results are shown, DCA will be tested in vivo in nude mice xenotransplanted with the same tumors, at doses of 25 mg / kg, 75 mg / kg or 125 mg / kg. The tumors will be measured by caliper, and after euthanasia will be collected, weighed and analyzed histologically. Thus we hope to advance into new anticancer therapies, obtaining important results that will allow the conduction of clinical trials in dogs in due course. (AU)