Abstract 4607: Chemoprevention of hepatocellular carcinoma with anthocyanin-rich black currant (Ribes nigrum L.) extract: in vitro and in vivo evidence

Abstract

Abstract Primary liver cancer, mostly hepatocellular carcinoma (HCC), represents the fifth most common malignancy and the third most common cause of cancer-related death worldwide. Although majority of newly diagnosed cases occur in Eastern Asia as well as sub-Saharan Africa, the incidence of HCC has been increasing steadily in Western countries, including the United States. In view of the severity of the disease and the limited treatment options available, a critical need exists for novel chemopreventive strategies which reduce the current morbidity and mortality associated with HCC. Natural dietary components, including fruits and vegetables, have drawn considerable attention due to their proven ability to affect carcinogenesis. Anthocyanins, a group of phytochemicals, are known to possess anticarcinogenic properties against several cancers, demonstrating potential for cancer prevention. Black currant (Ribes nigrum L.) fruits, recently termed “superfruits”, have high anthocyanin content. This fruit is known to possess potent antioxidant and anti-inflammatory properties. Although health benefits of black currant are known, limited evidence on antitumor effects of black currant exists with virtually no information on prevention of experimental carcinogenesis. The objective of the present study was to evaluate the potential antihepatocarcinogenic effects of anthocyanin-rich black currant skin extract (BCSE) against HepG2 human liver cancer cells as well as chemically-induced rat liver tumorigenesis. BCSE exhibited a potent cytotoxic effect on HepG2 cells with half maximal inhibitory concentration of 1.35 mg/mL. Treatment of rats with BCSE (100 or 500 mg/kg), started 4 weeks prior to and continued for 18 weeks following diethylnitrosamine (DENA)-initiated hepatocarcinogenesis, dose-dependently decreased the incidence, total number, multiplicity, size, and volume of preneoplastic hepatic nodules. The antihepatocarcinogenic effect of BCSE was supported by histopathological examination of hepatic sections. Immunohistochemical analysis of proliferating cell nuclear antigen and DNA fragmentation revealed BCSE-mediated inhibition of abnormal cell proliferation and induction of apoptosis in DENA-induced rat liver tumorigenesis respectively. BCSE also exerted an up-regulation of Bax and down-regulation of Bcl-2 expression at the translational level compared to DENA control. The results of the present investigation reveal, for the first time, that an anthocyanin-rich extract from black currant exerts a striking chemopreventive effect against hepatocellular carcinoma by inhibiting abnormal cell proliferation and inducing apoptosis through modulation of Bax/Bcl-2 ratio. These results along with a safety profile of BCSE encourage the development of black currant bioactive constituents as chemopreventive agents for human liver cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4607. doi:10.1158/1538-7445.AM2011-4607