Anthocyanin-rich black currant (Ribes nigrum L.) extract affords chemoprevention against diethylnitrosamine-induced hepatocellular carcinogenesis in rats.
Animals; Anthocyanins/*therapeutic use; Anticarcinogenic Agents/therapeutic use; Apoptosis/drug effects; bcl-2-Associated X Protein/metabolism; Cell Proliferation/drug effects; Chemoprevention; Diethylnitrosamine; Down-Regulation; Experimental/metabolism/pathology; Liver Neoplasms; Liver Neoplasms/chemically induced/*prevention & control; Liver/pathology; Male; Phenobarbital; Plant Extracts/*therapeutic use; Proliferating Cell Nuclear Antigen/metabolism; Proto-Oncogene Proteins c-bcl-2/metabolism; Rats; Ribes/chemistry; Sprague-Dawley; Up-Regulation
Anthocyanins are known to possess potent anticarcinogenic properties against several cancers thus demonstrating potential for cancer prevention. Black currant (Ribes nigrum L., Grossulariaceae) fruits have a high anthocyanin content. This "superfruit" is known to possess various pharmacological effects including alleviation of chronic oxidative stress and inflammation. In contrast to a large volume of literature on the health benefits of black currant, limited evidence on antitumor effects of black currant exists with virtually no data on the prevention of experimental carcinogenesis. In the current study, we have investigated the chemopreventive effects of an anthocyanin-rich black currant skin extract (BCSE) utilizing our well-characterized model of rat liver carcinogenesis. Initiation of hepatocarcinogenesis was done by intraperitoneal injection of diethylnitrosamine (DENA) followed by promotion with phenobarbital. The rats were exposed to dietary BCSE for 4 weeks prior to initiation, and the treatment was continued for 22 consecutive weeks. BCSE dose-dependently decreased the incidence, total number, multiplicity, size and volume of preneoplastic hepatic nodules. The antihepatocarcinogenic effect of BCSE was confirmed by histopathological examination of liver sections. Immunohistochemical analysis of proliferating cell nuclear antigen and DNA fragmentation revealed BCSE-mediated inhibition of abnormal cell proliferation and induction of apoptosis in
Bishayee Anupam; Mbimba Thomas; Thoppil Roslin J; Haznagy-Radnai Erzsebet; Sipos Peter; Darvesh Altaf S; Folkesson Hans G; Hohmann Judit
The Journal of nutritional biochemistry
2011
2011-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.jnutbio.2010.09.001" target="_blank" rel="noreferrer noopener">10.1016/j.jnutbio.2010.09.001</a>
Loss of FXR protects against diet-induced obesity and accelerates liver carcinogenesis in ob/ob mice.
Adipose Tissue; Adiposity/genetics; Animals; Brown/pathology; Carcinoma/etiology/*genetics; Cell Transformation; Cytoplasmic and Nuclear/*deficiency/genetics; Diet; Dietary Fats/metabolism; Energy Metabolism/genetics; Female; Gene Knockout Techniques; Glucose Intolerance/complications/genetics; High-Fat/*adverse effects; Intestinal Absorption; Knockout; Leptin/deficiency/genetics; Liver Neoplasms/etiology/*genetics; Liver/pathology; Male; Mice; Muscle; Neoplastic/genetics; Obese; Obesity/*etiology/genetics; Receptors; Sex Factors; Skeletal/metabolism; Weight Gain/genetics
Farnesoid X receptor (FXR) is known to play important regulatory roles in bile acid, lipid, and carbohydrate metabolism. Aged (\textgreater12 months old) Fxr(-/-) mice also develop spontaneous liver carcinomas. In this report, we used three mouse models to investigate the role of FXR deficiency in obesity. As compared with low-density lipoprotein receptor (Ldlr) knockout (Ldlr(-/-)) mice, the Ldlr(-/-)Fxr(-/-) double-knockout mice were highly resistant to diet-induced obesity, which was associated with increased expression of genes involved in energy metabolism in the skeletal muscle and brown adipose tissue. Such a striking effect of FXR deficiency on obesity on an Ldlr(-/-) background led us to investigate whether FXR deficiency alone is sufficient to affect obesity. As compared with wild-type mice, Fxr(-/-) mice showed resistance to diet-induced weight gain. Interestingly, only female Fxr(-/-) mice showed significant resistance to diet-induced obesity, which was accompanied by increased energy expenditure in these mice. Finally, we determined the effect of FXR deficiency on obesity in a genetically obese and diabetic mouse model. We generated ob(-/-)Fxr(-/-) mice that were deficient in both Leptin and Fxr. On a chow diet, ob(-/-)Fxr(-/-) mice gained less body weight and had reduced body fat mass as compared with ob/ob mice. In addition, we observed liver carcinomas in 43% of young (\textless11 months old) Ob(-/-)Fxr(-/-) mice. Together these data indicate that loss of FXR prevents diet-induced or genetic obesity and accelerates liver carcinogenesis under diabetic conditions.
Zhang Yanqiao; Ge Xuemei; Heemstra Lydia A; Chen Wei-Dong; Xu Jiesi; Smith Joseph L; Ma Huiyan; Kasim Neda; Edwards Peter A; Novak Colleen M
Molecular endocrinology (Baltimore, Md.)
2012
2012-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1210/me.2011-1157" target="_blank" rel="noreferrer noopener">10.1210/me.2011-1157</a>