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Predictive potential of natural compounds and their pathways of action in canine prostatic carcinoma: an in vitro model


Dog is the only mammal species, besides men, that spontaneously develop prostatic carcinoma (PCa), related to age, androgen hormones and pre-neoplastic lesions. These prostatic lesions are frequent in men, showing similarities in the pathological and molecular aspects, in both species. For that, dog is considered a good natural model for the study of the prostate carcinogenic process. Now a days, there are six cell culture linages from canine prostatic neoplasia, in Canada, Germany and USA. Never the less, these linages are not available for researches. Considering canine PCa treatment, there isn?t a well stablish treatment protocol, being castration the recommendation, although it is not really effective, since most of the canine PCa are androgen independent. Different chemotherapy and radiotherapy protocols have been indicated, but without good therapeutic response. The use of natural compounds has been increasing for cancer treatment and research, with good results. Based on these facts, and due to the importance of the dog, as a natural model for the study of human CPa, this research aims to stablish two canine prostatic cancer cell lines, as well as evaluate the efficacy of three natural compounds (Resveratrol, Viscum and melatonin) in anti-cancer effect ?in vitro? in the canine CPa cell lines. After achieving the IC50 for each drug, using large scale gene expression, we will evaluate genes networks and canonic pathways involved in the anti-tumoral treatment. Drivers genes from these pathways and networks will be selected and validated by RT-PCR. Drugs with synergic effect, based on the gene networks and canonic pathways, will be used in conjunction, to treat the cell lines. We hope to add knowledge of the anti-tumoral action of the natural compounds studied. In future "in vivo" experiments, the dog can be used in clinical trials, and the results shared with human medicine. This project has the support of a multidisciplinary and international group of researchers. (AU)

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