This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Holmes-McNary, M. Articles by Baldwin, A. S. Search for Related Content PubMed PubMed Citation Articles by Holmes-McNary, M. Articles by Baldwin, A. S., Jr.

Chemopreventive Properties of trans-Resveratrol Are Associated with Inhibition of Activation of the IB Kinase¹

Lineberger Comprehensive Cancer Center [M. H-M., A. S. B.] and Curriculum in Genetics and Molecular Biology [A. S. B.], University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295

trans-Resveratrol (Res), a phytoalexin found at high levels in grapes and in grape products such as red wine, has been shown to have anti-inflammatory and antioncogenic properties. Because the transcription factor nuclear factor B (NF-B) is involved in inflammatory diseases and oncogenesis, we tested whether Res could modulate NF-B activity. Res was shown to be a potent inhibitor of both NF-B activation and NF-B-dependent gene expression through its ability to inhibit IB kinase activity, the key regulator in NF-B activation, likely by inhibiting an upstream signaling component. In addition, Res blocked the expression of mRNA-encoding monocyte chemoattractant protein-1, a NF-B-regulated gene. Relative to cancer chemopreventive properties, Res induced apoptosis in fibroblasts after the induced expression of oncogenic H-Ras. Thus, Res is likely to function by inhibiting inflammatory and oncogenic diseases, at least in part, through the inhibition of NF-B activation by blocking IB kinase activity. These data may also explain aspects of the so-called "French paradox" that is associated with reduced mortality from coronary heart disease and certain cancers and provide a molecular rationale for the role of a potent chemopreventive compound in blocking the initiation of inflammation and oncogenesis.

This article has been cited by other articles:

				M. N. Chahine and G. N. Pierce Therapeutic Targeting of Nuclear Protein Import in Pathological Cell Conditions Pharmacol. Rev., September 1, 2009; 61(3): 358 - 372. [Abstract] [Full Text] [PDF]

				D. Zhang, L. Qiu, X. Jin, Z. Guo, and C. Guo Nuclear Factor-{kappa}B Inhibition by Parthenolide Potentiates the Efficacy of Taxol in Non-Small Cell Lung Cancer In vitro and In vivo Mol. Cancer Res., July 1, 2009; 7(7): 1139 - 1149. [Abstract] [Full Text] [PDF]

				A. Sharafkhaneh, S. Velamuri, V. Badmaev, C. Lan, and N. Hanania Review: The potential role of natural agents in treatment of airway inflammation Therapeutic Advances in Respiratory Disease, December 1, 2007; 1(2): 105 - 120. [Abstract] [PDF]

				T. Szkudelski Resveratrol-induced inhibition of insulin secretion from rat pancreatic islets: evidence for pivotal role of metabolic disturbances Am J Physiol Endocrinol Metab, October 1, 2007; 293(4): E901 - E907. [Abstract] [Full Text] [PDF]

				E.-O. Lee, H.-J. Lee, H.-S. Hwang, K.-S. Ahn, C. Chae, K.-S. Kang, J. Lu, and S.-H. Kim Potent inhibition of Lewis lung cancer growth by heyneanol A from the roots of Vitis amurensis through apoptotic and anti-angiogenic activities Carcinogenesis, October 1, 2006; 27(10): 2059 - 2069. [Abstract] [Full Text] [PDF]

				J. K. Kundu, Y. K. Shin, S. H. Kim, and Y.-J. Surh Resveratrol inhibits phorbol ester-induced expression of COX-2 and activation of NF-{kappa}B in mouse skin by blocking I{kappa}B kinase activity Carcinogenesis, July 1, 2006; 27(7): 1465 - 1474. [Abstract] [Full Text] [PDF]

				J. Mohan, A. A. Gandhi, B. C. Bhavya, R. Rashmi, D. Karunagaran, R. Indu, and T. R. Santhoshkumar Caspase-2 Triggers Bax-Bak-dependent and -independent Cell Death in Colon Cancer Cells Treated with Resveratrol J. Biol. Chem., June 30, 2006; 281(26): 17599 - 17611. [Abstract] [Full Text] [PDF]

				M. Sengottuvelan, P. Viswanathan, and N. Nalini Chemopreventive effect of trans-resveratrol - a phytoalexin against colonic aberrant crypt foci and cell proliferation in 1,2-dimethylhydrazine induced colon carcinogenesis Carcinogenesis, May 1, 2006; 27(5): 1038 - 1046. [Abstract] [Full Text] [PDF]

				K. R. Martin Targeting Apoptosis with Dietary Bioactive Agents Experimental Biology and Medicine, February 1, 2006; 231(2): 117 - 129. [Abstract] [Full Text] [PDF]

				J. E. Hoberg, A. E. Popko, C. S. Ramsey, and M. W. Mayo I{kappa}B Kinase {alpha}-Mediated Derepression of SMRT Potentiates Acetylation of RelA/p65 by p300 Mol. Cell. Biol., January 15, 2006; 26(2): 457 - 471. [Abstract] [Full Text] [PDF]

				C. A. Conover, L. K. Bale, S. C. Harrington, Z. T. Resch, M. T. Overgaard, and C. Oxvig Cytokine stimulation of pregnancy-associated plasma protein A expression in human coronary artery smooth muscle cells: inhibition by resveratrol Am J Physiol Cell Physiol, January 1, 2006; 290(1): C183 - C188. [Abstract] [Full Text] [PDF]

				H. S. Youn, J. Y. Lee, K. A. Fitzgerald, H. A. Young, S. Akira, and D. H. Hwang Specific Inhibition of MyD88-Independent Signaling Pathways of TLR3 and TLR4 by Resveratrol: Molecular Targets Are TBK1 and RIP1 in TRIF Complex J. Immunol., September 1, 2005; 175(5): 3339 - 3346. [Abstract] [Full Text] [PDF]

				S. Ghisletti, C. Meda, A. Maggi, and E. Vegeto 17{beta}-Estradiol Inhibits Inflammatory Gene Expression by Controlling NF-{kappa}B Intracellular Localization Mol. Cell. Biol., April 15, 2005; 25(8): 2957 - 2968. [Abstract] [Full Text] [PDF]

				H. Jiang, L. Zhang, J. Kuo, K. Kuo, S. C. Gautam, L. Groc, A. I. Rodriguez, D. Koubi, T. Jackson Hunter, G. B. Corcoran, et al. Resveratrol-induced apoptotic death in human U251 glioma cells Mol. Cancer Ther., April 1, 2005; 4(4): 554 - 561. [Abstract] [Full Text] [PDF]

				M. T. Yip-Schneider, H. Nakshatri, C. J. Sweeney, M. S. Marshall, E. A. Wiebke, and C. M. Schmidt Parthenolide and sulindac cooperate to mediate growth suppression and inhibit the nuclear factor-{kappa}B pathway in pancreatic carcinoma cells Mol. Cancer Ther., April 1, 2005; 4(4): 587 - 594. [Abstract] [Full Text] [PDF]

				P. Marchetti Natural medicine: a 'new frontier' in oncology? Ann. Onc., March 1, 2005; 16(3): 339 - 340. [Full Text] [PDF]

				M. Lun, P. L. Zhang, P. K. Pellitteri, A. Law, T. L. Kennedy, and R. E. Brown Nuclear Factor-kappaB Pathway as a Therapeutic Target in Head and Neck Squamous Cell Carcinoma: Pharmaceutical and Molecular Validation in Human Cell Lines Using Velcade and siRNA/NF-{kappa}B. Ann. Clin. Lab. Sci., January 1, 2005; 35(3): 251 - 258. [Abstract] [Full Text] [PDF]

				J.-L. Su, M.-T. Lin, C.-C. Hong, C.-C. Chang, S.-G. Shiah, C.-W. Wu, S.-T. Chen, Y.-P. Chau, and M.-L. Kuo Resveratrol induces FasL-related apoptosis through Cdc42 activation of ASK1/JNK-dependent signaling pathway in human leukemia HL-60 cells Carcinogenesis, January 1, 2005; 26(1): 1 - 10. [Abstract] [Full Text] [PDF]

				L. E. Donnelly, R. Newton, G. E. Kennedy, P. S. Fenwick, R. H. F. Leung, K. Ito, R. E. K. Russell, and P. J. Barnes Anti-inflammatory effects of resveratrol in lung epithelial cells: molecular mechanisms Am J Physiol Lung Cell Mol Physiol, October 1, 2004; 287(4): L774 - L783. [Abstract] [Full Text] [PDF]

				J. Leiro, E. Cano, F. M. Ubeira, F. Orallo, and M. L. Sanmartin In Vitro Effects of Resveratrol on the Viability and Infectivity of the Microsporidian Encephalitozoon cuniculi Antimicrob. Agents Chemother., July 1, 2004; 48(7): 2497 - 2501. [Abstract] [Full Text] [PDF]

				S.-Y. Sun, N. Hail Jr, and R. Lotan Apoptosis as a Novel Target for Cancer Chemoprevention J Natl Cancer Inst, May 5, 2004; 96(9): 662 - 672. [Abstract] [Full Text] [PDF]

				N. Osakabe, A. Yasuda, M. Natsume, and T. Yoshikawa Rosmarinic acid inhibits epidermal inflammatory responses: anticarcinogenic effect of Perilla frutescens extract in the murine two-stage skin model Carcinogenesis, April 1, 2004; 25(4): 549 - 557. [Abstract] [Full Text] [PDF]

				A. W. Opipari Jr., L. Tan, A. E. Boitano, D. R. Sorenson, A. Aurora, and J. R. Liu Resveratrol-induced Autophagocytosis in Ovarian Cancer Cells Cancer Res., January 15, 2004; 64(2): 696 - 703. [Abstract] [Full Text] [PDF]

				S. PERVAIZ Resveratrol: from grapevines to mammalian biology FASEB J, November 1, 2003; 17(14): 1975 - 1985. [Full Text] [PDF]

				A. J. Gescher and W. P. Steward Relationship between Mechanisms, Bioavailibility, and Preclinical Chemopreventive Efficacy of Resveratrol: A Conundrum Cancer Epidemiol. Biomarkers Prev., October 1, 2003; 12(10): 953 - 957. [Full Text] [PDF]

				Z. Estrov, S. Shishodia, S. Faderl, D. Harris, Q. Van, H. M. Kantarjian, M. Talpaz, and B. B. Aggarwal Resveratrol blocks interleukin-1{beta}-induced activation of the nuclear transcription factor NF-{kappa}B, inhibits proliferation, causes S-phase arrest, and induces apoptosis of acute myeloid leukemia cells Blood, August 1, 2003; 102(3): 987 - 995. [Abstract] [Full Text] [PDF]

				J. R. Stewart, M. C. Artime, and C. A. O'Brian Resveratrol: A Candidate Nutritional Substance for Prostate Cancer Prevention J. Nutr., July 1, 2003; 133(7): 2440S - 2443. [Abstract] [Full Text] [PDF]

				F. D. Ragione, V. Cucciolla, V. Criniti, S. Indaco, A. Borriello, and V. Zappia p21Cip1 Gene Expression Is Modulated by Egr1: A NOVEL REGULATORY MECHANISM INVOLVED IN THE RESVERATROL ANTIPROLIFERATIVE EFFECT J. Biol. Chem., June 20, 2003; 278(26): 23360 - 23368. [Abstract] [Full Text] [PDF]

				S. C. Pingle, J. F. Sanchez, D. M. Hallam, A. L. Williamson, S. B. Maggirwar, and V. Ramkumar Hypertonicity Inhibits Lipopolysaccharide-Induced Nitric Oxide Synthase Expression in Smooth Muscle Cells by Inhibiting Nuclear Factor {kappa}B Mol. Pharmacol., June 1, 2003; 63(6): 1238 - 1247. [Abstract] [Full Text] [PDF]

				Y. Bayon, M. A. Ortiz, F. J. Lopez-Hernandez, F. Gao, M. Karin, M. Pfahl, and F. J. Piedrafita Inhibition of I{kappa}B Kinase by a New Class of Retinoid-Related Anticancer Agents That Induce Apoptosis Mol. Cell. Biol., February 1, 2003; 23(3): 1061 - 1074. [Abstract] [Full Text]

				K. Ashikawa, S. Majumdar, S. Banerjee, A. C. Bharti, S. Shishodia, and B. B. Aggarwal Piceatannol Inhibits TNF-Induced NF-{kappa}B Activation and NF-{kappa}B-Mediated Gene Expression Through Suppression of I{kappa}B{alpha} Kinase and p65 Phosphorylation J. Immunol., December 1, 2002; 169(11): 6490 - 6497. [Abstract] [Full Text] [PDF]

				J. L. Evans, I. D. Goldfine, B. A. Maddux, and G. M. Grodsky Oxidative Stress and Stress-Activated Signaling Pathways: A Unifying Hypothesis of Type 2 Diabetes Endocr. Rev., October 1, 2002; 23(5): 599 - 622. [Abstract] [Full Text] [PDF]

				U. G. B. Haider, D. Sorescu, K. K. Griendling, A. M. Vollmar, and V. M. Dirsch Resveratrol Suppresses Angiotensin II-Induced Akt/Protein Kinase B and p70 S6 Kinase Phosphorylation and Subsequent Hypertrophy in Rat Aortic Smooth Muscle Cells Mol. Pharmacol., October 1, 2002; 62(4): 772 - 777. [Abstract] [Full Text] [PDF]

				A. V. Gasparian, Y. J. Yao, J. Lu, A. Y. Yemelyanov, L. A. Lyakh, T. J. Slaga, and I. V. Budunova Selenium Compounds Inhibit I{kappa}B Kinase (IKK) and Nuclear Factor-{kappa}B (NF-{kappa}B) in Prostate Cancer Cells Mol. Cancer Ther., October 1, 2002; 1(12): 1079 - 1087. [Abstract] [Full Text] [PDF]

				S. Banerjee, C. Bueso-Ramos, and B. B. Aggarwal Suppression of 7,12-Dimethylbenz(a)anthracene-induced Mammary Carcinogenesis in Rats by Resveratrol: Role of Nuclear Factor-{kappa}B, Cyclooxygenase 2, and Matrix Metalloprotease 9 Cancer Res., September 1, 2002; 62(17): 4945 - 4954. [Abstract] [Full Text] [PDF]

				H. Ferry-Dumazet, O. Garnier, M. Mamani-Matsuda, J. Vercauteren, F. Belloc, C. Billiard, M. Dupouy, D. Thiolat, J. P. Kolb, G. Marit, et al. Resveratrol inhibits the growth and induces the apoptosis of both normal and leukemic hematopoietic cells Carcinogenesis, August 1, 2002; 23(8): 1327 - 1333. [Abstract] [Full Text] [PDF]

				Y. M. Kim, J. Yun, C.-K. Lee, H. Lee, K. R. Min, and Y. Kim Oxyresveratrol and Hydroxystilbene Compounds. INHIBITORY EFFECT ON TYROSINASE AND MECHANISM OF ACTION J. Biol. Chem., May 3, 2002; 277(18): 16340 - 16344. [Abstract] [Full Text] [PDF]

				F. D'Acquisto, M. J. May, and S. Ghosh Inhibition of Nuclear Factor Kappa B (NF-B):: An Emerging Theme in Anti-Inflammatory Therapies Mol. Interv., February 1, 2002; 2(1): 22 - 35. [Abstract] [Full Text] [PDF]

				S. O. SHAHEEN, J. A. C. STERNE, R. L. THOMPSON, C. E. SONGHURST, B. M. MARGETTS, and P. G. J. BURNEY Dietary Antioxidants and Asthma in Adults . Population-based Case-Control Study Am. J. Respir. Crit. Care Med., November 15, 2001; 164(10): 1823 - 1828. [Abstract] [Full Text] [PDF]

				J. Gusman, H. Malonne, and G. Atassi A reappraisal of the potential chemopreventive and chemotherapeutic properties of resveratrol Carcinogenesis, August 1, 2001; 22(8): 1111 - 1117. [Abstract] [Full Text] [PDF]

				K. P. L. Bhat and J. M. Pezzuto Resveratrol Exhibits Cytostatic and Antiestrogenic Properties with Human Endometrial Adenocarcinoma (Ishikawa) Cells Cancer Res., August 1, 2001; 61(16): 6137 - 6144. [Abstract] [Full Text] [PDF]

				N. Ahmad, V. M. Adhami, F. Afaq, D. K. Feyes, and H. Mukhtar Resveratrol Causes WAF-1/p21-mediated G1-phase Arrest of Cell Cycle and Induction of Apoptosis in Human Epidermoid Carcinoma A431 Cells Clin. Cancer Res., May 1, 2001; 7(5): 1466 - 1473. [Abstract] [Full Text]

				M. Q. Holmes-McNary, A. S. Baldwin Jr., and S. H. Zeisel Opposing Regulation of Choline Deficiency-induced Apoptosis by p53 and Nuclear Factor kappa B J. Biol. Chem., October 26, 2001; 276(44): 41197 - 41204. [Abstract] [Full Text] [PDF]

				E. Heiss, C. Herhaus, K. Klimo, H. Bartsch, and C. Gerhauser Nuclear Factor kappa B Is a Molecular Target for Sulforaphane-mediated Anti-inflammatory Mechanisms J. Biol. Chem., August 17, 2001; 276(34): 32008 - 32015. [Abstract] [Full Text] [PDF]