Curcumin: a unique antioxidant offers a multimechanistic approach for management of hepatocellular carcinoma in rat model.

This study was designed to investigate the role of curcumin against hepatocellular carcinoma (HCC) induced in rats. Forty rats were divided into five groups. Group (1) was negative control. Groups (2), (4), and (5) were orally administrated N-nitrosodiethylamine for HCC induction, then group (2) was left untreated, and group (4) was treated orally with curcumin, while group (5) was intraperitoneally injected with doxorubicin. Group (3) was served as curcumin control group. Serum alpha-fetoprotein, alpha L-fucosidase and vascular endothelial growth factor levels were analyzed. Gamma glutamyl transferase (GGT) and heat shock protein gp96 (HSPgp96) gene expressions were detected by RT-PCR. The immunohistochemical analysis of proliferating cell nuclear antigen (PCNA) and Ki-67 expressions was performed. Apoptosis was detected using DNA fragmentation assay. Also, histological investigation of liver tissue was achieved. Untreated HCC group showed significant elevation in the studied biochemical markers and significant upregulation in GGT and HSPgp96 gene expression as well as marked increase in PCNA and Ki-67 expression. Furthermore, this group revealed no DNA fragmentation. Histological investigation of liver tissue sections in HCC group revealed a typical anaplasia. On the other hand, the curcumin-treated group showed a significant depletion in the studied tumor markers and a significant downregulation in GGT and HSPgp96 gene expression. Also, this group displayed remarkable decrease in PCNA and Ki-67 expression. Moreover, this group revealed an obvious DNA fragmentation. Interestingly, treatment with curcumin showed remarkable improvement in the histological features of liver tissue. This study revealed the promising therapeutic role of curcumin against hepatocellular carcinoma owing to its antiangiogenic, antiproliferative, and apoptotic effects.