Available online www.jocpr.com Journal of Chemical and Pharmaceutical Research, 2015, 7(4):913-921 Research Article ISSN : 0975-7384 CODEN(USA) : JCPRC5 913 Anticancer properties of resveratrol on chemically induced hepatocellular carcinoma in rats: Inhibition of metastasis and angiogenesis Abeer H. Abdel-Halim 1 , Amal A. Fyiad 1 , Mamdouh M. Ali *1 and Saeed M. Soliman 2 1 Biochemistry Department, Division of Genetic Engineering and Biotechnology, National Research Centre, Dokki, Giza, Egypt 2 Radiation Biology Department, National Centre for Radiation Research, Cairo, Egypt _____________________________________________________________________________________________ ABSTRACT Hepatocellular carcinoma (HCC) is one of the major health burdens and the fifth most common cancer worldwide. Although there are several drugs available to control cancer growth, there are fewer drugs presently available to specifically inhibit the metastasis of cancer cells or prevent its angiogenesis. The present study aimed to investigate the protective or therapeutic effect of resveratrol (natural phytoalexin) on diethylnitroseamine (DENA) induced hepatocarcinogenesis in rats. Rats were injected with a single dose DENA (200mg/kg b.w, i.p) only or with pre and post treatment of low and high doses of resveratrol (300mg/kg b.w and 450mg/kg b.w) respectively by feeding for 9 months. To elucidate the mechanism by which resveratrol exerts its function as anticancer agent, the following parameters were determined: aspartate and alanine aminotransferase (AST, ALT), alkaline phosphatase (ALP), total bilirubin as liver function test; vascular endothelial growth factor (VEGF) as a marker for angiogenesis and heparanase, elastase and matrixmetalloproteinases(MMPs) as markers of metastasis. Histopathological investigation was also confirmed. All parameters are elevated in DENA group, which confirmed by histopathological analysis where hepatic hemorrhages associated with necrosis, hyperchromatism, hyperplasia, proliferating hepatocytes were noticed. While the administration of resveratrol improved all biochemical and histopathological changes in post-treated groups more than pre-treated one, indicating that resveratrol may be a potent anticancer agent and its therapeutic effect is more potent than protective effect. Keywords: Hepatocellular carcinoma, Chemoprevention, Resveratrol, Angiogenesis, Metastasis. _____________________________________________________________________________________________ INTRODUCTION Hepatocellular carcinoma (HCC) is one of the most frequent tumors representing the fifth commonest malignancy worldwide and the third cause of mortality from cancer[1]. The vast majority of HCC cases is attributed to underlying hepatitis B and hepatitis C virus infection, but several other risk factors, e.g., excessive alcohol consumption, obesity, iron overload as well as environmental and chemical carcinogens are also involved in its etiology[2,3].The survival of patients with clinically apparent HCC is generally limited a few months. The majority of patients with symptoms of HCC have tumors that are not amenable to curative treatment because of the extensive involvement of the liver, invasion of the hepatic or portal vein and the presence of metastases [4,5]. In view of the limited treatment by surgical resection or liver transplantation and negative prognosis of liver cancer, preventive control approaches, notably chemoprevention has been considered to be the best strategy in lowering the present prevalence of the disease [6].