Tumor Biology

, Volume 36, Issue 3, pp 1667–1678 | Cite as

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

  • Hanaa H. Ahmed
  • Wafaa Gh. Shousha
  • Aziza B. Shalby
  • Hatem A. El-Mezayen
  • Nora N. Ismaiel
  • Nadia S. Mahmoud
Research Article


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.


Hepatocellular carcinoma Curcumin Angiogenesis Proliferation Apoptosis Rat 



The authors express sincere appreciation to Prof. Adel Bakeer kholoussy, Professor of Pathology, Faculty of Veterinary Medicine, Cairo University, for his kind cooperation in conducting histological investigations in this study.

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Hanaa H. Ahmed
    • 1
  • Wafaa Gh. Shousha
    • 2
  • Aziza B. Shalby
    • 1
  • Hatem A. El-Mezayen
    • 2
  • Nora N. Ismaiel
    • 3
  • Nadia S. Mahmoud
    • 1
  1. 1.Hormones Department, Medical Research DivisionNational Research CentreGizaEgypt
  2. 2.Chemistry Department, Faculty of ScienceHelwan UniversityCairoEgypt
  3. 3.Molecular Genetics and Enzymology Department, Human Genetics and Genome ResearchesNational Research CentreGizaEgypt

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