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Hemin inhibits cyclooxygenase-2 expression through nuclear factor-kappa B activation and ornithine decarboxylase expression in 12-O-tetradecanoylphorbol-13-acetate-treated mouse skin.
Mutat Res. 2008 Jul 03; 642(1-2):68-73.MR

Abstract

Inflammation induced by various stimuli has been found to be associated with increased risk for most types of human cancer. Inflammation facilitates the initiation of normal cells, as well as the growth of initiated cells and their progression to malignancy through production of proinflammatory cytokines and diverse reactive oxygen/nitrogen species. These also activate the signaling molecules that are involved in inflammation and carcinogenesis. Our previous studies have demonstrated that hemin inhibited 7,12-dimethylbenz[a]anthracene (DMBA)-induced bacterial mutagenesis and oxidative DNA damage, reduced the level of DNA-DMBA adduct and 12-O-tetradecanoylphorobl-13-acetate (TPA)-induced tumor formation in DMBA-initiated ICR mouse skin, and inhibited myeloperoxidase and ornithine decarboxylase (ODC) activity and H(2)O(2) formation in TPA-treated mouse skin. In the present study, to further elucidate the molecular mechanisms underlying the chemopreventive activity of hemin, its effect on the expression of ODC and cyclooxygenase (COX)-2, and the activation of nuclear factor-kappa B (NF-kappaB) and mitogen-activated protein kinases (MAPKs) regulating these proteins were explored in mouse skin with TPA-induced inflammation. Topically applied hemin inhibited ear edema and epidermal thickness in mice treated with TPA. Pretreatment with hemin reduced the expression of ODC and COX-2, and also reduced NF-kappaB activation in TPA-stimulated mouse skin. In addition, hemin suppressed the TPA-induced activation of extracellular signal-regulated protein kinase (ERK) and p38 MAPK in a dose-dependent manner. Taken together, hemin inhibited TPA-induced COX-2 expression by altering NF-kappaB signaling pathway via ERK and p38 MAPK, as well as TPA-induced ODC expression in mouse skin. Thereby, hemin may be an attractive candidate for a chemopreventive agent.

Authors+Show Affiliations

Department of Oral Biology, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18534633

Citation

Park, Jae Hee, et al. "Hemin Inhibits Cyclooxygenase-2 Expression Through Nuclear Factor-kappa B Activation and Ornithine Decarboxylase Expression in 12-O-tetradecanoylphorbol-13-acetate-treated Mouse Skin." Mutation Research, vol. 642, no. 1-2, 2008, pp. 68-73.
Park JH, Lee CK, Hwang YS, et al. Hemin inhibits cyclooxygenase-2 expression through nuclear factor-kappa B activation and ornithine decarboxylase expression in 12-O-tetradecanoylphorbol-13-acetate-treated mouse skin. Mutat Res. 2008;642(1-2):68-73.
Park, J. H., Lee, C. K., Hwang, Y. S., Park, K. K., & Chung, W. Y. (2008). Hemin inhibits cyclooxygenase-2 expression through nuclear factor-kappa B activation and ornithine decarboxylase expression in 12-O-tetradecanoylphorbol-13-acetate-treated mouse skin. Mutation Research, 642(1-2), 68-73. https://doi.org/10.1016/j.mrfmmm.2008.04.004
Park JH, et al. Hemin Inhibits Cyclooxygenase-2 Expression Through Nuclear Factor-kappa B Activation and Ornithine Decarboxylase Expression in 12-O-tetradecanoylphorbol-13-acetate-treated Mouse Skin. Mutat Res. 2008 Jul 3;642(1-2):68-73. PubMed PMID: 18534633.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hemin inhibits cyclooxygenase-2 expression through nuclear factor-kappa B activation and ornithine decarboxylase expression in 12-O-tetradecanoylphorbol-13-acetate-treated mouse skin. AU - Park,Jae Hee, AU - Lee,Chang Ki, AU - Hwang,Young Sun, AU - Park,Kwang-Kyun, AU - Chung,Won-Yoon, Y1 - 2008/04/24/ PY - 2008/01/04/received PY - 2008/04/06/revised PY - 2008/04/16/accepted PY - 2008/6/7/pubmed PY - 2008/8/21/medline PY - 2008/6/7/entrez SP - 68 EP - 73 JF - Mutation research JO - Mutat Res VL - 642 IS - 1-2 N2 - Inflammation induced by various stimuli has been found to be associated with increased risk for most types of human cancer. Inflammation facilitates the initiation of normal cells, as well as the growth of initiated cells and their progression to malignancy through production of proinflammatory cytokines and diverse reactive oxygen/nitrogen species. These also activate the signaling molecules that are involved in inflammation and carcinogenesis. Our previous studies have demonstrated that hemin inhibited 7,12-dimethylbenz[a]anthracene (DMBA)-induced bacterial mutagenesis and oxidative DNA damage, reduced the level of DNA-DMBA adduct and 12-O-tetradecanoylphorobl-13-acetate (TPA)-induced tumor formation in DMBA-initiated ICR mouse skin, and inhibited myeloperoxidase and ornithine decarboxylase (ODC) activity and H(2)O(2) formation in TPA-treated mouse skin. In the present study, to further elucidate the molecular mechanisms underlying the chemopreventive activity of hemin, its effect on the expression of ODC and cyclooxygenase (COX)-2, and the activation of nuclear factor-kappa B (NF-kappaB) and mitogen-activated protein kinases (MAPKs) regulating these proteins were explored in mouse skin with TPA-induced inflammation. Topically applied hemin inhibited ear edema and epidermal thickness in mice treated with TPA. Pretreatment with hemin reduced the expression of ODC and COX-2, and also reduced NF-kappaB activation in TPA-stimulated mouse skin. In addition, hemin suppressed the TPA-induced activation of extracellular signal-regulated protein kinase (ERK) and p38 MAPK in a dose-dependent manner. Taken together, hemin inhibited TPA-induced COX-2 expression by altering NF-kappaB signaling pathway via ERK and p38 MAPK, as well as TPA-induced ODC expression in mouse skin. Thereby, hemin may be an attractive candidate for a chemopreventive agent. SN - 0027-5107 UR - https://www.unboundmedicine.com/medline/citation/18534633/Hemin_inhibits_cyclooxygenase_2_expression_through_nuclear_factor_kappa_B_activation_and_ornithine_decarboxylase_expression_in_12_O_tetradecanoylphorbol_13_acetate_treated_mouse_skin_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0027-5107(08)00093-6 DB - PRIME DP - Unbound Medicine ER -