Inhibitory effects of oligonol on phorbol ester-induced tumor promotion and COX-2 expression in mouse skin: NF-κB and C/EBP as potential targets
Inhibitory effects of oligonol on phorbol ester-induced tumor promotion and COX-2 expression in mouse skin: NF-κB and C/EBP as potential targets
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DOI：
10.1016/j.canlet.2008.07.039
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发表时间：
2009-01-08
期刊：
影响因子：
9.7
通讯作者：
Surh, Young Joon
中科院分区：
文献类型：
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作者：
Kundu, Joydeb Kumar;Hwang, Dal-Mi;Surh, Young Joon
植物多酚具有抗氧化和抗炎活性，因此是预防癌症的潜在候选物质。本研究旨在评价儿茶素类低聚物低聚物低聚醇在原型癌促进剂12-O-十四烷基佛波醇-13-醋酸酯(TPA)刺激下的抗炎和抗肿瘤活性。低聚醇可显著抑制TPA诱导的环氧合酶-2(COX-2)的表达。低聚酚通过阻断磷酸化和随后降解TPA处理的小鼠皮肤中的I kappaBα来减少核因子kappaB(NF-kappaB)的核转移和DNA结合。此外，低聚醇抑制TPA诱导的小鼠皮肤中CCAAT/增强子结合蛋白(C/EBP)的DNA结合。低聚醇预处理还可减弱细胞外信号调节蛋白激酶-1/2(ERK1/2)和p38丝裂原活化蛋白(MAP)的磷酸化和/或催化活性。此外，p38 MAP激酶抑制剂SB203580，而不是MEK抑制剂U0126，可阻断TPA诱导的C/EBP的DNA结合。此外，低聚醇还能降低7，12-二甲基苯并[a]菲(DMBA)诱导和TPA诱导的小鼠皮肤乳头状瘤和鳞状细胞癌的发生率和多样性，延长荷瘤小鼠的存活时间。与DMBA+TPA单独治疗相比，低聚醇预处理分别降低乳头状瘤和癌组织中增殖细胞核抗原的水平和COX-2的表达。综上所述，上述研究结果表明，寡糖醇通过调节MAP激酶来阻断核因子-kappaB和C/EBP的激活，从而抑制TPA诱导的COX-2的表达，从而抑制化学诱导的小鼠皮肤肿瘤的发生。(C)2008爱思唯尔爱尔兰有限公司。保留所有权利。
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.