Tumor Biology

, Volume 36, Issue 3, pp 1763–1771 | Cite as

Curcumin ameliorate DENA-induced HCC via modulating TGF-β, AKT, and caspase-3 expression in experimental rat model

  • Mekky M. M. AbouziedEmail author
  • Heba M. Eltahir
  • Mohamed A. Abdel Aziz
  • Nagwa S. Ahmed
  • Ahmed A. Abd El-Ghany
  • Ebtihal A. Abd El-Aziz
  • Hekmat O. Abd El-Aziz
Research Article


Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. In laboratory animal models, diethylnitrosamine (DENA) is a well-known agent that has a potent hepatocarcinogenic effect that is used to induce HCC. As curcumin has a potent anti-inflammatory effect with strong therapeutic potential against a variety of cancers, our present study aims to investigate its curative effects and the possible mechanisms of action against DENA-induced HCC in male rats. Investigation of biochemical and molecular parameters of HCC animal model liver showed an overexpression of TGF-β and Akt proteins accompanied with a significant reduction of the proapoptotic marker caspase-3. DENA-induced hepatic cellular injury resulted also in a significant increase in liver function marker enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lipid peroxides in this group. Curcumin treatment partially reversed DENA-induced damage as it reduced the overexpression of the angiogenic and anti-apoptotic factors TGF-β and Akt and improved caspase-3 expression. Also, it could partially normalize the serum values of liver marker enzymes and lipid peroxidation and improve liver architecture. Curcumin shows a unique chemotherapeutic effect in reversing DENA-induced HCC in rat model. This effect is possibly mediated through its proapoptotic, antioxidant, anti-angiogenic, as well as antimitotic effects. It interferes and modulates cell signaling pathways and hence turns death signals and apoptosis on within tumor cells.


Apoptosis Angiogenesis TGF-β Akt Curcumin Diethylnitrosamine Hepatocellular carcinoma 





Endothelial growth factor


Fibroblast growth factor


Hepatocellular carcinoma




Matrix metalloproteinase-9


Reverse transcriptase Polymerase Chain Reaction


Sodium dodecyl sulfate–poly acrylamide gel electrophoresis


Transforming growth factor beta


Reactive oxygen species


Thiobarbituric acid


Vascular endothelial growth factor



This work was supported by Deanship of Scientific Research, Taibah University, El- Madinah El-Munawarah, P.O. Box 30001-Saudi Arabia, Faculty of Pharmacy Al-azhar University Assuit Branch-Egypt, and Faculty of Pharmacy Minia University, Mina, Egypt.

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Mekky M. M. Abouzied
    • 1
    • 2
    Email author
  • Heba M. Eltahir
    • 1
  • Mohamed A. Abdel Aziz
    • 3
  • Nagwa S. Ahmed
    • 4
  • Ahmed A. Abd El-Ghany
    • 3
  • Ebtihal A. Abd El-Aziz
    • 5
  • Hekmat O. Abd El-Aziz
    • 6
  1. 1.Department of Pharmacology and Toxicology, College of PharmacyTaibah UniversityEl- Madinah El-MunawarahSaudi Arabia
  2. 2.Department of Biochemistry, Faculty of PharmacyMinia UniversityMiniaEgypt
  3. 3.Department of Biochemistry, Faculty of PharmacyAl-Azhar UniversityAssiut branchEgypt
  4. 4.Department of Biochemistry, Faculty of MedicineSohag UniversitySohagEgypt
  5. 5.Department of Physiology, Faculty of MedicineAssiut UniversityAssuitEgypt
  6. 6.Department of Histology, Faculty of MedicineSohag UniversitySohagEgypt

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