Journal
CANCER LETTERS
Volume 273, Issue 1, Pages 86-97Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2008.07.039
Keywords
Oligonol; Chemoprevention; Mouse skin; Cyclooxygenase-2; MAPK; NF-kappa B; C/EBP
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Funding
- Research Institute of the Complementary and Alternative Medicine
- Seoul National University
- SRC Program [R71-2007-107-00000-0]
- National Research Laboratory Fund
- Korea Science and Engineering Foundation
- Ministry of Science and Technology, Republic of Korea
- Brain Korea (BK)-21
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Plant polyphenols possess anti-oxidant and anti-inflammatory activities and are hence potential candidates for preventing cancer. The present study was aimed at evaluating the anti-inflammatory and anti-tumor promoting activity of oligonol, a formulation of catechin-type oligomers, in mouse skin stimulated with a proto-type tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Pretreatment of mouse skin with oligonol significantly inhibited TPA-induced expression of cyclooxygenase-2 (COX-2). Oligonol diminished nuclear translocation and DNA binding of nuclear factor-kappaB (NF-kappa B) via blockade of phosphorylation and subsequent degradation of I kappa B alpha in TPA-treated mouse skin. Moreover, oligonol suppressed TPA-induced DNA binding of CCAAT/enhancer-binding protein (C/EBP) in mouse skin. Oligonol pretreatment also attenuated the phosphorylation and/or catalytic activities of extracellular signal-regulated protein kinase-1/2 (ERK1/2) and p38 mitogen-activated protein (MAP) kinase. Moreover, p38 MAP kinase inhibitor SB203580, but not the MEK inhibitor U0126, negated TPA-induced DNA binding of C/EBP. In addition, oligonol reduced the incidence and the multiplicity of papillomas and squamous cell carcinomas in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated and TPA-promoted mouse skin, and prolonged the survival of tumor-bearing mice. Pretreatment with oligonol diminished the levels of proliferating cell nuclear antigen and expression of COX-2 in papillomas and carcinomas, respectively, as compared to DMBA plus TPA treatment alone. Taken together, the above findings suggest that oligonol inhibits TPA-induced COX-2 expression by blocking the activation of NF-kappa B and C/EBP via modulation of MAP kinases and suppresses chemically induced mouse skin tumorigenesis. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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