Black tea polyphenols target matrix metalloproteinases, RECK, proangiogenic molecules and histone deacetylase in a rat hepatocarcinogenesis model.
BACKGROUND
The aim of this study was to evaluate the chemopreventive effects of black tea polyphenols (Polyphenon-B) on markers of invasion and angiogenesis during dimethylaminoazobenzene (DAB)-induced hepatocarcinogenesis.


METHODS
Male Sprague-Dawley rats were divided into four groups. The rats in groups 1 and 2 were given 0.06% DAB in the diet for 3 months followed by the normal diet. The rats in group 2 received in addition 0.05% Polyphenon-B in the basal diet. The group 3 animals were given 0.05% Polyphenon-B alone in the basal diet. The group 4 animals served as the control.


RESULTS
The dietary administration of DAB induced well-differentiated hepatocellular carcinomas (HCC) that showed increased expression of the markers of invasion, angiogenesis and epigenetic histone deacetylation compared with the controls. The administration of Polyphenon-B significantly reduced the incidence of DAB-induced hepatomas as evidenced by modulation of the markers of invasion (matrix metalloproteinase, MMP-2, MMP-9, tissue inhibitor of matrix metalloproteinase, TIMP-2, and reversion-inducing cysteine rich protein with Kazal motifs RECK) and angiogenesis (hypoxia inducible factor 1alpha, HIF1alpha, vascular endothelial growth factor, VEGF, and VEGF receptor, VEGFR1) as well as the expression of histone deacetylase HDAC-1.


CONCLUSIONS
The results of the present study provide evidence that Polyphenon-B has potential as a chemopreventive agent.
Murugan
R Senthil
RS
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India. s_nagini@yahoo.com, snlabau@gmail.com.
Vinothini
G
G
Hara
Y
Y
Nagini
S
S
D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D004195:Disease Models, Animal; D058851:GPI-Linked Proteins; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013662:Tea / Q000737:chemistry*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D042501:Angiogenic Proteins; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D010636:Phenols; D012333:RNA, Messenger; C529735:Reck protein, rat; D013662:Tea; D025521:Tumor Suppressor Proteins; C506663:polyphenon B; D020782:Matrix Metalloproteinases; D006655:Histone Deacetylases