Carcinogenesis Advance Access originally published online on July 4, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Carcinogenesis, Vol. 24, No. 9, 1515-1524,
September 2003
© 2003 Oxford University Press
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION |
Curcumin inhibits phorbol ester-induced expression of cyclooxygenase-2 in mouse skin through suppression of extracellular signal-regulated kinase activity and NF-
B activation
1 College of Pharmacy, College of Medicine, Seoul National University, Seoul 151-741, South Korea
2 Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, Seoul 151-741, South Korea
3 To whom correspondence should be addressed Email: surh{at}plaza.snu.ac.kr
Recently, there have been considerable efforts to search for naturally occurring substances for the intervention of carcinogenesis. Many components derived from dietary or medicinal plants have been found to possess substantial chemopreventive properties. Curcumin, a yellow coloring ingredient of turmeric (Curcuma longa L., Zingiberaceae), has been shown to inhibit experimental carcinogenesis and mutagenesis, but molecular mechanisms underlying its chemopreventive activities remain unclear. In the present work, we assessed the effects of curcumin on 12-O- tetradecanoylphorbol-13-acetate (TPA)-induced expression of cyclooxygenase-2 (COX-2) in female ICR mouse skin. Topical application of the dorsal skin of female ICR mice with 10 nmol TPA led to maximal induction of cox-2 mRNA and protein expression at 
1 and 4 h, respectively. When applied topically onto shaven backs of mice 30 min prior to TPA, curcumin inhibited the expression of COX-2 protein in a dose-related manner. Immunohistochemical analysis of TPA-treated mouse skin revealed enhanced expression of COX-2 localized primarily in epidermal layer, which was markedly suppressed by curcumin pre-treatment. Curcumin treatment attenuated TPA- stimulated NF-
B activation in mouse skin, which was associated with its blockade of degradation of the inhibitory protein IB
and also of subsequent translocation of the p65 subunit to nucleus. TPA treatment resulted in rapid activation via phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein (MAP) kinases, which are upstream of NF-B. The MEK1/2 inhibitor U0126 strongly inhibited NF-B activation, while p38 inhibitor SB203580 failed to block TPA-induced NF-B activation in mouse skin. Furthermore, U0126 blocked the IB phosphorylation by TPA, thereby blocking the nuclear translocation of NF-B. Curcumin inhibited the catalytic activity of ERK1/2 in mouse skin. Taken together, suppression of COX-2 expression by inhibiting ERK activity and NF-B activation may represent molecular mechanisms underlying previously reported antitumor promoting effects of this phytochemical in mouse skin tumorigenesis.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. M. Ansari, J. E. Rundhaug, and S. M. Fischer Multiple Signaling Pathways Are Responsible for Prostaglandin E2-Induced Murine Keratinocyte Proliferation Mol. Cancer Res., June 1, 2008; 6(6): 1003 - 1016. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Garg, A. G. Ramchandani, and G. B. Maru Curcumin decreases 12-O-tetradecanoylphorbol-13-acetate-induced protein kinase C translocation to modulate downstream targets in mouse skin Carcinogenesis, June 1, 2008; 29(6): 1249 - 1257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-C. Lee, J. K. Kundu, D.-M. Hwang, H.-K. Na, and Y.-J. Surh Humulone inhibits phorbol ester-induced COX-2 expression in mouse skin by blocking activation of NF-{kappa}B and AP-1: I{kappa}B kinase and c-Jun-N-terminal kinase as respective potential upstream targets Carcinogenesis, July 1, 2007; 28(7): 1491 - 1498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Y. Chung, J. H. Park, M. J. Kim, H. O. Kim, J. K. Hwang, S. K. Lee, and K. K. Park Xanthorrhizol inhibits 12-O-tetradecanoylphorbol-13-acetate-induced acute inflammation and two-stage mouse skin carcinogenesis by blocking the expression of ornithine decarboxylase, cyclooxygenase-2 and inducible nitric oxide synthase through mitogen-activated protein kinases and/or the nuclear factor-{kappa}B Carcinogenesis, June 1, 2007; 28(6): 1224 - 1231. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Davis, E. A. Murphy, M. D. Carmichael, M. R. Zielinski, C. M. Groschwitz, A. S. Brown, J. D. Gangemi, A. Ghaffar, and E. P. Mayer Curcumin effects on inflammation and performance recovery following eccentric exercise-induced muscle damage Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2007; 292(6): R2168 - R2173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-M. Park, A. Kim, J.-H. Oh, and A.-S. Chung Methylseleninic acid inhibits PMA-stimulated pro-MMP-2 activation mediated by MT1-MMP expression and further tumor invasion through suppression of NF-{kappa}B activation Carcinogenesis, April 1, 2007; 28(4): 837 - 847. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.-M. Hwang, J. K. Kundu, J.-W. Shin, J.-C. Lee, H. J. Lee, and Y.-J. Surh cis-9,trans-11-Conjugated linoleic acid down-regulates phorbol ester-induced NF-{kappa}B activation and subsequent COX-2 expression in hairless mouse skin by targeting I{kappa}B kinase and PI3K-Akt Carcinogenesis, February 1, 2007; 28(2): 363 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ohori, H. Yamakoshi, M. Tomizawa, M. Shibuya, Y. Kakudo, A. Takahashi, S. Takahashi, S. Kato, T. Suzuki, C. Ishioka, et al. Synthesis and biological analysis of new curcumin analogues bearing an enhanced potential for the medicinal treatment of cancer. Mol. Cancer Ther., October 1, 2006; 5(10): 2563 - 2571. [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]
|
|
|
|
 |
|
 K. W. Lee, J. K. Kundu, S. O. Kim, K.-S. Chun, H. J. Lee, and Y.-J. Surh Cocoa Polyphenols Inhibit Phorbol Ester-Induced Superoxide Anion Formation in Cultured HL-60 Cells and Expression of Cyclooxygenase-2 and Activation of NF-{kappa}B and MAPKs in Mouse Skin In Vivo J. Nutr., May 1, 2006; 136(5): 1150 - 1155. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-J. Surh, J. K. Kundu, H.-K. Na, and J.-S. Lee Redox-Sensitive Transcription Factors as Prime Targets for Chemoprevention with Anti-Inflammatory and Antioxidative Phytochemicals J. Nutr., December 1, 2005; 135(12): 2993S - 3001S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. KULKARNI, Y. T. GHEBREMARIAM, and G. J. KOTWAL Curcumin Inhibits the Classical and the Alternate Pathways of Complement Activation Ann. N.Y. Acad. Sci., November 1, 2005; 1056(1): 100 - 112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Moon, W. C. Glasgow, and T. E. Eling Curcumin Suppresses Interleukin 1{beta}-Mediated Microsomal Prostaglandin E Synthase 1 by Altering Early Growth Response Gene 1 and Other Signaling Pathways J. Pharmacol. Exp. Ther., November 1, 2005; 315(2): 788 - 795. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Yang, G. P. Lim, A. N. Begum, O. J. Ubeda, M. R. Simmons, S. S. Ambegaokar, P. P. Chen, R. Kayed, C. G. Glabe, S. A. Frautschy, et al. Curcumin Inhibits Formation of Amyloid {beta} Oligomers and Fibrils, Binds Plaques, and Reduces Amyloid in Vivo J. Biol. Chem., February 18, 2005; 280(7): 5892 - 5901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-Y. Lee, J.-W. Shin, K.-S. Chun, K.-K. Park, W.-Y. Chung, Y.-J. Bang, J.-H. Sung, and Y.-J. Surh Antitumor promotional effects of a novel intestinal bacterial metabolite (IH-901) derived from the protopanaxadiol-type ginsenosides in mouse skin Carcinogenesis, February 1, 2005; 26(2): 359 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D Lambert, J. Hong, G.-y. Yang, J. Liao, and C. S Yang Inhibition of carcinogenesis by polyphenols: evidence from laboratory investigations Am. J. Clinical Nutrition, January 1, 2005; 81(1): 284S - 291S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. W. LEE, K.-S. CHUN, J.-S. LEE, K.-S. KANG, Y.-J. SURH, and H. J. LEE Inhibition of Cyclooxygenase-2 Expression and Restoration of Gap Junction Intercellular Communication in H-ras-Transformed Rat Liver Epithelial Cells by Caffeic Acid Phenethyl Ester Ann. N.Y. Acad. Sci., December 1, 2004; 1030(1): 501 - 507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hong, M. Bose, J. Ju, J.-H. Ryu, X. Chen, S. Sang, M.-J. Lee, and C. S. Yang Modulation of arachidonic acid metabolism by curcumin and related {beta}-diketone derivatives: effects on cytosolic phospholipase A2, cyclooxygenases and 5-lipoxygenase Carcinogenesis, September 1, 2004; 25(9): 1671 - 1679. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-S. Chun, S.-H. Kim, Y.-S. Song, and Y.-J. Surh Celecoxib inhibits phorbol ester-induced expression of COX-2 and activation of AP-1 and p38 MAP kinase in mouse skin Carcinogenesis, May 1, 2004; 25(5): 713 - 722. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Kundu, H.-K. Na, K.-S. Chun, Y.-K. Kim, S. J. Lee, S. S. Lee, O.-S. Lee, Y.-C. Sim, and Y.-J. Surh Inhibition of Phorbol Ester-Induced COX-2 Expression by Epigallocatechin Gallate in Mouse Skin and Cultured Human Mammary Epithelial Cells J. Nutr., November 1, 2003; 133(11): 3805S - 3810. [Abstract] [Full Text] [PDF]
|
|