Targeting canine mammary tumours via gold nanoparticles functionalized with promising Co(II) and Zn(II) compounds.

BACKGROUND: Despite continuous efforts, the treatment of canine cancer has still to deliver effective strategies. For example, traditional chemotherapy with doxorubicin and/or docetaxel does not significantly increase survival in dogs with canine mammary tumors (CMTs). AIMS: Evaluate the efficiency of two metal compounds [Zn(DION)2 ]Cl (TS262, DION = 1,10-phenanthroline-5,6-dione) and [CoCl(H2 O)(DION)2 ][BF4 ] (TS265) and novel nanovectorizations designed to improve the anti-cancer efficacy of these compounds in a new CMT derived cell line (FR37-CMT). MATERIALS AND METHODS: FR37-CMT cells were exposed to different concentrations of TS262 and TS265 and two new nanoparticle systems and cellular viability was determined. These nanosystems are composed of polyethylene-glycol, bovine-serum-albumin and TS262 or TS265 (NanoTS262 or NanoTS265, respectively). RESULTS: In FR37-CMT, TS262 and TS265 displayed IC50 values well below those displayed by doxorubicin and cisplatin. The nanovectorizations further decreased the IC50 values. DISCUSSION: TS262 and TS265 proved to be effective against FR37-CMT cells and more effective than of doxorubicin and cisplatin. The Nanosystems efficiently delivered the cytotoxic cargo inducing a significant reduction of cell viability in FR37-CMT cell line when compared to the free compounds. CONCLUSIONS: TS262 and TS265 are compounds with potential in the treatment of CMTs. NanoTS262 and NanoTS265 demonstrate that such simple nanovectorization via gold nanoparticles shows tremendous potential as anti-cancer formulations, which may easily be expanded to suit other cargo.

Immortalization and characterization of a new canine mammary tumour cell line FR37-CMT.

Here we describe the establishment of a new canine mammary tumour (CMT) cell line, FR37-CMT that does not show dependence on female hormonal signaling to induce tumour xenografts in NOD-SCID mice. FR37-CMT cell line has a stellate or fusiform shape, displays the ability to reorganize the collagen matrix, expresses vimentin, CD44 and shows the loss of E-cadherin which is considered a fundamental event in epithelial to mesenchymal transition (EMT). The up-regulation of ZEB1, the detection of phosphorylated ERK1/2 and the downregulation of DICER1 and miR-200c are also in accordance with the mesenchymal characteristics of FR37-CMT cell line. FR37-CMT shows a higher resistance to cisplatin (IC50 >50 µM) and to doxorubicin (IC50 >5.3 µM) compared with other CMT cell lines. These results support the use of FR37-CMT as a new CMT model that may assist the understanding of the molecular mechanisms underlying EMT, CMT drug resistance, fostering the development of novel therapies targeting CMT.