Eugenol Precludes Cutaneous Chemical Carcinogenesis in Mouse by Preventing Oxidative Stress and Inflammation and by Inducing Apoptosis
Eugenol Precludes Cutaneous Chemical Carcinogenesis in Mouse by Preventing Oxidative Stress and Inflammation and by Inducing Apoptosis
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DOI：
10.1002/mc.20601
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发表时间：
2010-03-01
影响因子：
4.6
通讯作者：
Alam, M. Sarwar
中科院分区：
文献类型：
--
作者：
Kaur, Gurpreet;Athar, Mohammad;Alam, M. Sarwar
本研究旨在探讨丁香酚对皮肤癌的保护作用及其机制。皮肤肿瘤开始应用160 nmol DMBA和促进每周两次应用8.5 nmol TPA 28周。所有小鼠均在13周的促进期发生肿瘤。然而，在用30 μ L丁香酚预处理的小鼠中，直到肿瘤促进8周（遵循抗启动方案）和14周（遵循抗促进方案）才检测到肿瘤。PCNA和TUNEL免疫组化结果显示丁香酚可改善肿瘤细胞增殖和促进肿瘤细胞凋亡。丁香酚的效果进行了评估的具体阶段的癌。用DMBA启动导致p53表达的显著上调，伴随着表皮细胞中p21（WAF 1）水平的增加，表明对DNA的损伤的诱导。然而，丁香酚预处理导致这些基因的过表达，这可能有助于刺激启动细胞的凋亡。为了确定丁香酚抗肿瘤促进活性的分子机制，研究了其对肿瘤促进和炎症标志物的影响：ODC活性和NOS和考克斯-2表达，以及促炎细胞因子（IL-6，TNF-α和PGE（2））的水平。丁香酚明显抑制所有。丁香酚还抑制上游信号分子：NF-κ B，其调节这些基因的表达。TPA诱导的皮肤GSH和抗氧化酶库的耗竭也被丁香酚排除。从这些结果，可以得出结论，丁香酚显着防止化学诱导的皮肤癌，并可能凭借其抗增殖，抗炎和抗氧化活性的作用。(C)2009威利-利斯公司
The present study was designed to investigate the protective efficacy of eugenol against skin cancer and probe into the mechanistic aspects. Skin tumors were initiated by applying 160 nmol DMBA and promoted by twice weekly applications of 8.5 nmol TPA for 28 wk. All mice developed tumors by 13 wk of promotion. However, in mice pretreated with 30 mu L eugenol, no tumors were detected until 8 wk (following anti-initiation protocol) and until 14 wk (following antipromotion protocol) of tumor promotion. PCNA and TUNEL immunohistochemistry of tumors revealed eugenol to ameliorate cell proliferation and elevate apoptosis respectively. The effect of eugenol was assessed on specific stages of carcinogenesis. Initiation with DMBA led to a significant upregulation of p53 expression with a concomitant increase in p21(WAF1) levels in epidermal cells indicating induction of damage to the DNA. However, pretreatment with eugenol led to overexpression of these genes, which probably helped stimulate apoptosis of the initiated cells. To ascertain the molecular mechanisms implicated in the antitumor promoting activity of eugenol, its effect was investigated on markers of tumor promotion and inflammation: ODC activity and NOS and COX-2 expression, and on levels of proinflammatory cytokines (IL-6, TNF-alpha, and PGE(2)). Eugenol markedly inhibited all. Eugenol also inhibited the upstream signaling molecule: NF-kappa B, which regulates the expression of these genes. TPA-induced depletion of cutaneous GSH and antioxidant enzymes armory was also precluded by eugenol. From these results, it could be concluded that eugenol markedly protects against chemically induced skin cancer and acts possibly by virtue of its antiproliferative, anti-inflammatory, and antioxidant activities. (C) 2009 Wiley-Liss, Inc.