Inhibition by curcumin of diethylnitrosamine-induced hepatic hyperplasia, inflammation, cellular gene products and cell-cycle-related proteins in rats.
Curcumin (CCM), a major yellow pigment of turmeric obtained from powdered rhizomes of the plant Curcuma longa Linn, is commonly used as coloring agent in foods, drugs and cosmetics. In this study we report that gavage administration of 200 mg/kg or 600 mg/kg CCM effectively suppressed diethylnitrosamine (DEN)-induced liver inflammation and hyperplasia in rats, as evidenced by histopathological examination. Immunoblotting analysis showed that CCM strongly inhibited DEN-mediated the increased expression of oncogenic p21(ras) and p53 proteins in liver tissues of rats. In cell-cycle-related proteins, CCM selectively reduced the expression of proliferating cell nuclear antigen (PCNA), cyclin E and p34(cdc2), but not Cdk2 or cyclin D1. Moreover, CCM also inhibited the DEN-induced increase of transcriptional factor NF-kappa B. However, CCM failed to affect DEN-induced c-Jun and c-Fos expression. It has become widely recognized that the development of human hepatocellular carcinoma (HCC) is predominantly due to the chronic inflammation by virus, bacteria or chemical. Our results suggest a potential role for CCM in the prevention of HCC.
Chuang
S E
SE
Division of Cancer Research, National Health Research Institute, Taipei, Taiwan.
Cheng
A L
AL
Lin
J K
JK
Kuo
M L
ML
D000818:Animals; D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000517:prevention & control; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D003474:Curcumin / Q000627:therapeutic use*; D004052:Diethylnitrosamine / Q000633:toxicity; D006965:Hyperplasia / Q000188:drug therapy / Q000517:prevention & control; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D015689:Oncogene Protein p21(ras) / Q000037:antagonists & inhibitors / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000378:metabolism
D018797:Cell Cycle Proteins; D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; D004052:Diethylnitrosamine; D016203:CDC2 Protein Kinase; D015689:Oncogene Protein p21(ras); D003474:Curcumin