Question

Updates on the biochemical and molecular mechanisms of n-nitrosodiethylamine-induced hepatocellular carcinoma: promising therapeutic role of punica granatum peel extract

Answer 1

his study was undertaken to elucidate the underlying biochemical and molecular mechanisms in favour of N-nitrosodiethylamine-induced hepatocellular carcinoma. Also, the aim of this work was extended to explore the efficacy of Punica granatum peel extract in retrogression of hepatocellular carcinoma (HCC) in rats. HCC group experienced significant elevation in the studied biochemical markers in serum paralleled by significant downregulation of ING-3 gene expression level and upregulation of Foxp-1 gene expression level in liver. Moreover, HCC group exhibited remarkable increase in β-catenin, survivin and Ki-67 expression in the liver as shown in the immunohistochemical analysis. Furthermore, histopathological investigation of liver tissue sections of rats in HCC group revealed typical anaplasia. In contrast, the treatment of HCC groups with Punica granatum peel extract resulted in significant depletion in the liver enzymes activity in association with significant reduction in the studied tumor markers and angiogenic markers. Upregulation of ING-3 and downregulation of Foxp-1 gene expression level in liver have been also detected due to treatment of HCC groups with Punica granatum peel extract. Furthermore, these groups displayed marked decrease in β-catenin, survivin and Ki-67 expression in the liver. Interestingly, treatment with Punica granatum peel extract elicited marked improvement in the histological feature of liver tissue of HCC groups. In conclusion, the present study indicated that the carcinogenic potency of N-nitrosodiethylamine targeted multiple systems on the cellular and molecular levels. Also, the present findings shed light on the promising anticancer activity of Punica granatum peel extract in recession of hepatocellular carcinoma induced chemically in the experimental model through its antiangiogenic, apoptotic and antiproliferative effciency.