Sodium dichloroacetate attenuates the growth of B16-F10 melanoma in vitro and in vivo: an opportunity for drug repurposing.

Sodium dichloroacetate (DCA) is a metabolic regulator used to treat diabetes. Since DCA inhibits pyruvate dehydrogenase kinase, decreasing lactic acid formation, it can reverse the Warburg effect in cancer cells, promoting apoptosis. Therefore, this study aimed to investigate the potential of DCA as a drug repurposing candidate for the treatment of melanoma. For the in-vitro assay, murine B16-F10 melanoma cells were treated with 0.5, 1, 5, 10, 20 or 50 mM DCA for 3 days, analyzed with the crystal violet method. The in-vivo effect of DCA was evaluated in B16-F10 tumor-bearing C57BL/6 mice treated with different doses of DCA (0, 25, 75 or 150 mg/kg) by gavage for 10 days, followed by measurement of tumor volume. Upon necropsy, representative slices of lung, liver, kidney, spleen and intestine were collected, processed and submitted for histopathological examination. The DCA concentrations of 10, 20 and 50 mM reduced B16-F10 cell viability after 48 and 72 h of treatment, whereas 20 and 50 mM were effective after 24 h of treatment. A significant reduction in tumor growth was observed in B16-F10 melanoma bearing mice at all doses, with no change in body weight or histology. DCA attenuates the growth of B16-F10 melanoma in vitro and in vivo, without systemic toxic effects. Therefore, DCA is a candidate for drug repurposing against melanomas.

Establishment of primary mixed cell cultures from spontaneous canine mammary tumors: Characterization of classic and new cancer-associated molecules.

There are many factors which make canine cancer like cancer in humans. The occurrence of spontaneous mammary tumors in pet dogs, tumor genetics, molecular targets and exposure to the same environmental risk factors are among these factors. Therefore, the study of canine cancer can provide useful information to the oncology field. This study aimed to establish and characterize a panel of primary mixed cell cultures obtained from spontaneous canine mammary tumors. Eight established cell cultures obtained from one normal mammary gland, one complex adenoma, one mixed adenoma, two complex carcinomas and two mixed carcinomas were analyzed. The gene expression levels of classic molecular cancer players such as fibroblast growth factor receptor (FGFR) 2, breast cancer (BRCA) 1, BRCA2 and estrogen receptor (ESR) 1 were evaluated. For the first time, three orphan nuclear receptors, estrogen-related receptors (ERRs) α, ß and γ were studied in canine mammary cancer. The highest expression level of ERRα was observed in complex carcinoma-derived cell culture, while the highest levels of ERRß and γ were observed in cells derived from a mixed carcinoma. Meanwhile, complex carcinomas presented the highest levels of expression of ESR1, BRCA1 and FGFR2 among all samples. BRCA2 was found exclusively in complex adenoma. The transcription factor GATA3 had its highest levels in mixed carcinoma samples and its lowest levels in complex adenoma. Proliferation assays were also performed to evaluate the mixed cell cultures response to ER ligands, genistein and DES, both in normoxia and hypoxic conditions. Our results demonstrate that morphological and functional studies of primary mixed cell cultures derived from spontaneous canine mammary tumors are possible and provide valuable tool for the study of various stages of mammary cancer development.