Red wine and black tea polyphenols modulate the expression of cycloxygenase-2, inducible nitric oxide synthase and glutathione-related enzymes in azoxymethane-induced f344 rat colon tumors.
Polyphenolic compounds extracted from red wine (WE) and black tea (BT), 50 mg/(kg. d), inhibit the promotion phase of the colon carcinogenesis process induced by azoxymethane (AOM) in rodents. To investigate possible mechanisms of this protective activity, we evaluated by RT-PCR the gene expression of cycloxygenase-2 (COX-2), inducible NO synthase (iNOS), gamma-glutamylcysteine synthetase (gamma-GCS) and two isoforms of glutathione S-transferase (GST), GST-P and GST-M2, in 30 AOM-induced tumors and in the corresponding normal colon mucosa. AOM-induced colon tumors had significantly greater GST-P, GST-M2, COX-2 and iNOS gene expression than the corresponding normal mucosa. However, tumors harvested from rats treated with BT (P < 0.05) and WE (P < 0.01) polyphenols had a lower GST-P mRNA level than tumors from controls. Treatment with WE polyphenols induced a similar inhibitory effect on the colon tumor overexpression of GST-M2 (P < 0.01), COX-2 (P < 0.05) and iNOS (P < 0.05). In the normal mucosa, rats treated with BT polyphenols had greater gamma-GCS expression than controls (P < 0.01). Our results provide evidence that WE and BT polyphenols modulate COX-2, iNOS and glutathione-related gene expression in tumors, suggesting that these compounds have possible chemotherapeutic activity.
Luceri
Cristina
C
Department of Pharmacology, University of Florence, 50139 Florence, Italy. c.luceri@server1.pharm.unifi.it
Caderni
Giovanna
G
Sanna
Anna
A
Dolara
Piero
P
D000818:Animals; D003106:Colon / Q000187:drug effects / Q000201:enzymology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids; D015971:Gene Expression Regulation, Enzymologic; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000235:genetics / Q000378:metabolism*; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*; D059808:Polyphenols; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013662:Tea / Q000737:chemistry; D014920:Wine / Q000032:analysis
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007527:Isoenzymes; D010636:Phenols; D011108:Polymers; D059808:Polyphenols; D012333:RNA, Messenger; D013662:Tea; D019001:Nitric Oxide Synthase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D005982:Glutathione Transferase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione