Ellagic Acid Holds Promise Against Hepatocellular Carcinoma in an Experimental Model: Mechanisms of Action

Abstract

This research work was initiated to explore the efficacy of ellagic acid in mitigation of hepatocarcinogenesis in rats. Rats were distributed into 4 groups; negative control, hepatocellular carcinoma (HCC), doxorubicin and ellagic acid. Serum alpha-fetoprotein (AFP), glypican-3 (GPC-3), signal transducer and activator of transcription 3 (STAT3) and suppressors of cytokine signaling 3 (SOCS3) levels were assayed by ELISA. Immunohistochemical examination of hepatic VEGF expression was also conducted, along with histological procedures for examination of liver tissue sections. Significant elevation in serum AFP, GPC-3 and STAT3 levels with a significant drop in SOCS3 were observed in the HCC group. In contrast, the treated groups showed significant decline in serum AFP, GPC-3 and STAT3 levels and significant increase in SOCS3. Additionally, the HCC group declared mild positive immunoreaction for VEGF in hepatocytes while treatment with doxorubicin or ellagic acid was associated with a negative immunoreaction for VEGF. These results were supported by histological examination of liver tissue. The obtained findings suggested that ellagic acid may have beneficial chemopreventive role against hepatocarcinogenesis through its apoptotic, antiangiogenic and antiproliferative activities.