Morin--a
bioflavonoid is a naturally available dietary agent believed to impede
cancer promotion and progression. The present study was conducted to decipher, in vivo, the role of
morin on the expression of
matrix metalloproteinases,
cyclooxygenase (COX)-2 and
nuclear factor kappa B (NF-kappaB)-p65 during
diethylnitrosamine (DEN)-induced hepatocarcinogenesis in Wistar albino rats.
Reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed that administration of DEN (200 mg/kg bodyweight in
drinking water) to experimental animals caused
inflammation of the liver due to up-regulation of NF-kappaB-p65 and COX-2. RT-PCR and immunoblot analysis also revealed that the oral supplementation of
morin (500 ppm in diet) to DEN-induced
hepatocellular carcinoma rats down-regulated the expression of COX-2 and NF-kappaB-p65, thereby preventing
inflammation and angiogenesis mediated hepatocellular
carcinogenesis. Further, immunohistological analysis for NF-kappaB-p65 nuclear localization confirms the above observations.
Gelatin zymography was performed for
matrix metalloproteinase MMP-2 and MMP-9 expression to confirm their role in angiogenesis in DEN induced
hepatocellular carcinoma and its modulation by
morin. Both MMP-2 and MMP-9 levels were found to be increased in DEN-induced animals when compared to control. MMP-2 and MMP-9 levels were down-regulated in
morin post-treated animals when compared to DEN-induced animals favouring prevention of angiogenesis. In conclusion, our findings indicate that
morin possessed anti-inflammatory and anti-
cancer properties favouring suppression of DEN-induced
hepatocellular carcinoma.