title: Suppression of the inflammatory cascade is implicated in resveratrol chemoprevention of experimental hepatocarcinogenesis.
abstract: OBJECTIVE
  Resveratrol, present in grapes and red wine, has been found to prevent diethylnitrosamine (DENA)-initiated rat liver tumorigenesis, though the chemopreventive mechanisms are not completely elucidated. The current study was designed to explore whether the antiinflammatory properties of resveratrol play a role in its antihepatocarcinogenic action.
  
  
  METHODS
  Liver samples were harvested from a 20-week chemopreventive study in which resveratrol (50, 100 and 300 mg/kg) was shown to inhibit DENA-induced hepatocyte nodules in Sprague-Dawley rats in a dose-responsive manner. Hepatic preneoplastic and inflammatory markers, namely heat shock protein (HSP70), cyclooxygenase-2 (COX-2) and nuclear factor-kappaB (NF-kappaB), were studied using immunohistochemical as well as Western blot techniques.
  
  
  RESULTS
  Resveratrol dose-dependently suppressed DENA-induced increased expressions of hepatic HSP70 and COX-2. Resveratrol also attenuated the DENA-mediated translocation of NF-kappaB p65 from the cytosol to the nucleus with stabilization of inhibitory kappaB.
  
  
  CONCLUSIONS
  The present findings indicate that resveratrol exerts chemoprevention of hepatocarcinogenesis possibly through antiinflammatory effects during DENA-evoked rat liver carcinogenesis by suppressing elevated levels of HSP70, COX-2 as well as NF-kappaB. These beneficial effects combined with an excellent safety profile encourage the development of resveratrol for chemoprevention and intervention of human HCC that remains a devastating disease.
authors.affiliation: Department of Pharmaceutical Sciences Cancer Therapeutics and Chemoprevention Emphasis Group, Northeastern Ohio Universities Colleges of Medicine and Pharmacy, 4209 State Route 44, Rootstown Ohio, 44272, USA. abishayee@neoucom.edu
authors.forename: Anupam
authors.initials: A
authors.lastname: Bishayee
authors.forename: Abhijeet
authors.initials: A
authors.lastname: Waghray
authors.forename: Kendra F
authors.initials: KF
authors.lastname: Barnes
authors.forename: Thomas
authors.initials: T
authors.lastname: Mbimba
authors.forename: Deepak
authors.initials: D
authors.lastname: Bhatia
authors.forename: Malay
authors.initials: M
authors.lastname: Chatterjee
authors.forename: Altaf S
authors.initials: AS
authors.lastname: Darvesh
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D018890:Chemoprevention; D051546:Cyclooxygenase 2 / Q000276:immunology; D004052:Diethylnitrosamine; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control*; D016328:NF-kappa B / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000627:therapeutic use*
chemical_list: D016588:Anticarcinogenic Agents; D018840:HSP70 Heat-Shock Proteins; D016328:NF-kappa B; D013267:Stilbenes; D004052:Diethylnitrosamine; D051546:Cyclooxygenase 2; D000077185:Resveratrol
references.citation: Cancer Lett. 2008 Oct 8;269(2):243-61
references.pmid: 18550275
references.citation: J Lab Clin Med. 2002 Apr;139(4):234-43
references.pmid: 12024111
references.citation: Dig Dis. 2009;27(2):80-92
references.pmid: 19546545
references.citation: Cell Res. 2008 Mar;18(3):334-42
references.pmid: 18301380
references.citation: Exp Clin Cardiol. 2006 Fall;11(3):217-25
references.pmid: 18651034
references.citation: Ann N Y Acad Sci. 2009 Feb;1155:206-21
references.pmid: 19250206
references.citation: Gastroenterology. 2004 Nov;127(5 Suppl 1):S27-34
references.pmid: 15508094
references.citation: Lancet. 2003 Dec 6;362(9399):1907-17
references.pmid: 14667750
references.citation: Cancer Prev Res (Phila). 2009 May;2(5):409-18
references.pmid: 19401532
references.citation: Hepatology. 1999 Mar;29(3):688-96
references.pmid: 10051469
references.citation: Mol Carcinog. 1989;2(5):233-6
references.pmid: 2690852
references.citation: Cell. 1995 Nov 3;83(3):493-501
references.pmid: 8521479
references.citation: Clin Cancer Res. 2009 Jan 15;15(2):425-30
references.pmid: 19147746
references.citation: Mol Nutr Food Res. 2009 Jan;53(1):115-28
references.pmid: 19072742
references.citation: Clin Cancer Res. 2001 May;7(5):1325-32
references.pmid: 11350902
references.citation: Pharmacol Res. 2009 May;59(5):330-7
references.pmid: 19416633
references.citation: Nature. 2003 Sep 11;425(6954):191-6
references.pmid: 12939617
references.citation: World J Gastroenterol. 2006 Aug 28;12(32):5113-21
references.pmid: 16937518
references.citation: Mol Carcinog. 2008 Oct;47(10):797-805
references.pmid: 18381589
references.citation: Asian Pac J Cancer Prev. 2008 Apr-Jun;9(2):295-8
references.pmid: 18712978
references.citation: Inflamm Allergy Drug Targets. 2007 Sep;6(3):168-73
references.pmid: 17897053
references.citation: Cancer Res. 1986 Oct;46(10):5106-11
references.pmid: 3756868
references.citation: Clin Cancer Res. 2005 Aug 1;11(15):5645-50
references.pmid: 16061884
references.citation: Anticancer Res. 2009 Feb;29(2):539-44
references.pmid: 19331200
references.citation: Mol Cancer Ther. 2008 Dec;7(12):3751-60
references.pmid: 19074850
references.citation: Cancer Prev Res (Phila). 2010 Jun;3(6):753-63
references.pmid: 20501860
references.citation: Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7384-8
references.pmid: 1380156
references.citation: Nucleic Acids Res. 1983 Mar 11;11(5):1475-89
references.pmid: 6828386
references.citation: Cancer Prev Res (Phila). 2009 Mar;2(3):200-8
references.pmid: 19258539
references.citation: J Natl Cancer Inst. 2000 Oct 4;92(19):1564-72
references.pmid: 11018092
references.citation: J Biol Chem. 1994 Feb 18;269(7):4705-8
references.pmid: 7508926
references.citation: Chem Biol Interact. 2009 May 15;179(2-3):131-44
references.pmid: 19073162
references.citation: Eur J Cancer Prev. 2009 Feb;18(1):13-25
references.pmid: 19077560
references.citation: Ann N Y Acad Sci. 2009 Feb;1155:293-9
references.pmid: 19250220
references.citation: Biochem Pharmacol. 2006 May 14;71(10):1397-421
references.pmid: 16563357
references.citation: Cancer Lett. 2008 Oct 8;269(2):315-25
references.pmid: 18467024
references.citation: J Cancer Res Clin Oncol. 2009 Aug;135(8):969-81
references.pmid: 19399516
references.citation: Hepatology. 2007 Aug;46(2):590-7
references.pmid: 17661407
references.citation: Anticancer Res. 2003 Nov-Dec;23(6C):4921-6
references.pmid: 14981946
references.citation: Lab Invest. 1987 Jan;56(1):4-22
references.pmid: 3025514
references.citation: Biochem Biophys Res Commun. 1994 Aug 30;203(1):190-9
references.pmid: 8074655
references.citation: Mol Cells. 2004 Feb 29;17(1):35-8
references.pmid: 15055524
references.citation: Crit Rev Clin Lab Sci. 2000 Oct;37(5):431-502
references.pmid: 11078056
references.citation: Arch Biochem Biophys. 2009 Jun 15;486(2):95-102
references.pmid: 19514131
references.citation: J Korean Med Sci. 2005 Oct;20(5):829-34
references.pmid: 16224158
references.citation: Nat Immunol. 2002 Mar;3(3):221-7
references.pmid: 11875461
references.citation: Cancer Res. 2007 Oct 15;67(20):9844-51
references.pmid: 17942915
references.citation: Acta Pharmacol Sin. 2007 Sep;28(9):1331-42
references.pmid: 17723167
references.citation: J Nutr Sci Vitaminol (Tokyo). 2004 Feb;50(1):61-5
references.pmid: 15228220
references.citation: Semin Liver Dis. 2005;25(2):143-54
references.pmid: 15918143
references.citation: Cancer Sci. 2008 Jun;99(6):1109-16
references.pmid: 18429957
references.citation: Science. 1993 Mar 5;259(5100):1409-10
references.pmid: 8451637
references.citation: Gastroenterology. 2004 Nov;127(5 Suppl 1):S310-8
references.pmid: 15508099
references.citation: CA Cancer J Clin. 2005 Mar-Apr;55(2):74-108
references.pmid: 15761078
references.citation: J Appl Toxicol. 2009 Mar;29(2):91-100
references.pmid: 18937212
references.citation: Mol Nutr Food Res. 2008 Jun;52 Suppl 1:S62-70
references.pmid: 18551458
references.citation: Biochem Pharmacol. 2006 Nov 30;72(11):1439-52
references.pmid: 16920072
references.citation: Cancer Res. 2000 Jul 1;60(13):3477-83
references.pmid: 10910059
references.citation: Curr Med Chem. 2008;15(11):1044-71
references.pmid: 18473802
references.citation: Cancer. 2003 Aug 15;98(4):661-7
references.pmid: 12910508
references.citation: Carcinogenesis. 1984 Nov;5(11):1381-93
references.pmid: 6386215
references.citation: J Appl Toxicol. 2008 Jan;28(1):35-43
references.pmid: 17429801
references.citation: Cancer Treat Rev. 2010 Feb;36(1):43-53
references.pmid: 19910122
references.citation: Anticancer Res. 2004 Sep-Oct;24(5A):2783-840
references.pmid: 15517885
references.citation: Carcinogenesis. 2008 Aug;29(8):1639-47
references.pmid: 18579559
references.citation: Mol Cell Biochem. 2008 Jun;313(1-2):53-61
references.pmid: 18373278
references.citation: Hepatology. 2003 Jan;37(1):198-207
references.pmid: 12500205
references.citation: Nutrition. 2009 Nov-Dec;25(11-12):1169-76
references.pmid: 19818280
references.citation: World J Gastroenterol. 2005 Apr 14;11(14):2072-9
references.pmid: 15810071
references.citation: Biochim Biophys Acta. 2000 Mar 27;1470(2):M69-78
references.pmid: 10722929
references.citation: Cancer Treat Rev. 2006 Feb;32(1):28-44
references.pmid: 16337744
references.citation: Lancet Oncol. 2009 Oct;10(10):967-74
references.pmid: 19767240
references.citation: Chem Biol Interact. 2009 Aug 14;180(3):353-9
references.pmid: 19539802
references.citation: J Gastroenterol Hepatol. 2001 Dec;16(12):1329-35
references.pmid: 11851828