title: Curcumin ameliorate DENA-induced HCC via modulating TGF-β, AKT, and caspase-3 expression in experimental rat model.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, El- Madinah El-Munawarah, P.O. Box 30001, Saudi Arabia, m_meky2001@yahoo.com.
authors.forename: Mekky M M
authors.initials: MM
authors.lastname: Abouzied
authors.forename: Heba M
authors.initials: HM
authors.lastname: Eltahir
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Abdel Aziz
authors.forename: Nagwa S
authors.initials: NS
authors.lastname: Ahmed
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Abd El-Ghany
authors.forename: Ebtihal A
authors.initials: EA
authors.lastname: Abd El-Aziz
authors.forename: Hekmat O
authors.initials: HO
authors.lastname: Abd El-Aziz
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism*; D003474:Curcumin / Q000494:pharmacology*; D004052:Diethylnitrosamine; D004195:Disease Models, Animal; D004347:Drug Interactions; D043384:Glutamyl Aminopeptidase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta; D004052:Diethylnitrosamine; D000410:Alanine Transaminase; D051057:Proto-Oncogene Proteins c-akt; D043384:Glutamyl Aminopeptidase; D053148:Caspase 3; D003474:Curcumin