Red and White Wine Lees Show Inhibitory Effects on Liver Carcinogenesis.

SCOPE: Wine has shown anticarcinogenic benefits in hepatocarcinoma and polyphenols seem to be responsible for these effects. Wine lees are the sediments produced during fermentation and they endow wine with organoleptic and physicochemical properties. However, the anticarcinogenic role of these compounds is still unknown. Thus, the purpose of this work is to determine the phytochemical profiles of wine lees and then to analyze their anticarcinogenic effect and DNA methylation on a model of hepatocarcinogenesis. METHODS AND RESULTS: The phytochemical composition of lees is determined by the Folin-Ciocalteu method and high-performance liquid chromatography. An in vivo study using a diethyl nitrosamine-hepatocarcinogenesis-induced model is performed to investigate the hepatoprotective properties of different doses of wine lees. For the DNA methylation analysis, a bisulfite-based method is used. Both types of lees mostly contain pyrogallol, gallic, and syringic acid with a high content of catechins in red lees. The carcinogen hypermethylates the Alu-M2 repetitive sequence and white lees decreases the hypermethylation at all tested concentrations. Low concentration of red and white lees and high concentration of white lees significantly improve the hepatocellular architecture and decrease the mitotic index in the murine model. CONCLUSION: These findings suggest that wine lees are promising agents for chemoprevention of hepatocarcinoma.

PDGFR-α, PDGFR-ß, VEGFR-2 and CD117 expression in canine mammary tumours and evaluation of the in vitro effects of toceranib phosphate in neoplastic mammary cell lines.

Canine mammary tumours (CMTs) are one of the most common malignancies in bitches. Platelet-derived growth factor receptor (PDGFR) α and ß, vascular endothelial growth factor receptor-2 (VEGFR-2) and CD117 are tyrosine kinase receptors involved in several tumours and represent suitable targets for specific therapy with toceranib phosphate. The purpose of this study was to evaluate the expression of these receptors in the pathogenesis and progression of CMTs. PDGFRα, PDGFRß, VEGFR-2 and CD117 were expressed in 46/83 (55.4 per cent), 33/83 (39.8 per cent), 46/83 (55.4 per cent) and 32/83 (38.5 per cent) of CMTs, respectively. Immunohistochemical results showed a statistically significant loss of PDGFRα and PDGFRß expression in simple carcinomas compared with complex/mixed carcinomas. Protein expression by western blot revealed specific bands corresponding to PDGFRα and VEGFR-2 in 3/7 and in 1/7 cell lines. Moreover, in vitro treatment showed that toceranib phosphate weakly reduced cell proliferation in one canine mammary cell line. Before considering TKR inhibitors for possible therapeutic approaches, actually further studies are necessary to evaluate the effect of these drugs on CMTs in vivo.

Demethylating and anti-hepatocarcinogenic potential of hesperidin, a natural polyphenol of Citrus juices.

Hepatocellular carcinoma (HCC) is a neoplasia representing the fifth most common malignancy worldwide and the third cause of death from cancer. Diets with high content in fruits and vegetables are widely recommended for their health-promoting properties, among them, the protection against diabetes, cancer, and cardiovascular diseases. Hesperidin is the most important phenol in the orange fruit with well-known health benefits. Diet components have been used as possible modulator agents of DNA methylation in cancer cells and epigenetic therapy against their harmful effects could be a potential tool in chemotherapy. The purpose of the present study was to evaluate the methylation patterns induced by hesperidin in HL60 cell line as an in vitro model in order to analyze its chemopreventive effects in epigenetic cancer therapies. A parallel in vivo pilot experience using a rat diethyl nitrosamine hepatocarcinogenesis-induced model was carried out to validate the therapeutic efficacy of this orange flavonol. Results showed that: (i) Hesperidin is cytotoxic in a dose-dependent manner and the IC50 was 12.5 mM; (ii) Hesperidin exerts a significant hypomethylating effect on the LINE-1 sequence (up to 47% hypomethylation at 12.5 mM) and on the ALU-M2 repetitive sequences (up to 32% at 6 mM) in HL60 tumor cells. (iii) Hesperidin does not affect the rat body and liver weight and it is able to reduce the diethyl nitrosamine-induced nodules at 1,000, 500, and 250 ppm. In conclusion, hesperidin could be proposed as a candidate molecule in chemoprevention in epigenetic therapy purposes.