Skin tumor promotion by argemone oil/alkaloid in mice: Evidence for enhanced cell proliferation, ornithine decarboxylase, cyclooxygenase-2 and activation of MAPK/NF-κB pathway
Skin tumor promotion by argemone oil/alkaloid in mice: Evidence for enhanced cell proliferation, ornithine decarboxylase, cyclooxygenase-2 and activation of MAPK/NF-κB pathway
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DOI：
10.1016/j.fct.2009.09.029
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发表时间：
2010-01-01
影响因子：
4.3
通讯作者：
Das, Mukul
中科院分区：
文献类型：
--
作者：
Ansari, Kausar M.;Das, Mukul
食用被阿贡油（AO）污染的食用油会导致“流行性水臌”。以前，我们已经证明AD和分离的血根碱具有遗传毒性和皮肤肿瘤启动活性。在此，我们评估了AO/sanguinarine生物碱的促肿瘤潜力，并探讨了其分子机制。单次局部应用AO （50-400 μ mol/只小鼠）或血根碱生物碱（1.5-12.0 μ mol/只小鼠）可显著增加(i)鸟氨酸脱羧酶（ODC）活性，（ii） DNA中[H-3]-胸苷的摄取，（iii）环氧化酶-2 (COX-2)，增殖细胞核抗原（PCNA）和ODC蛋白表达，（iv）细胞外信号调节激酶（ERK）1/2， c-jun- n-末端激酶（JNK）1/2和p38丝裂原活化蛋白（MAP）激酶的磷酸化。(v) nf - κ B活化增加，（vi）深色基底角质形成细胞无显著增加。随后，在7,12-二甲基苯并(a)蒽（DMBA）启动小鼠中，分别以AD和血根碱生物碱作为完全或I期或II期肿瘤启动子进行检测时，以AO （0.1 ml）或分离血根碱（1.5 μ mol）作为II期肿瘤启动子时，肿瘤发生率增加，肿瘤体负荷增加，小鼠肿瘤发生率升高。然而，当AO或血碱生物碱作为完全或I期肿瘤促进剂进行测试时，未发现肿瘤。这些结果表明AO/ sanguinarine生物碱在II期水平具有促进肿瘤的潜力，涉及MAPK/NF-kappa B通路。2009爱思唯尔有限公司版权所有。
Consumption of argemone oil (AO) contaminated edible oil causes "Epidemic Dropsy". Previously, we have shown that AD and isolated sanguinarine possess genotoxicity and skin tumor initiating activity. Here, we evaluate tumor-promoting potential of AO/sanguinarine alkaloid and investigate the molecular mechanisms involved therein. Single topical application of AO (50-400 mu l/mouse) or sanguinarine alkaloid (1.5-12.0 mu mol/mouse) afforded significant increase in (i) ornithine decarboxylase (ODC) activity, (ii) uptake of [H-3]-thymidine in DNA, (iii) cyclooxygenase-2 (COX-2), proliferating cell nuclear antigen (PCNA) and ODC protein expressions, (iv) phosphorylation of extracellular signal-regulated kinase (ERK)1/2, c-jun-N-terminal kinase (JNK)1/2 and p38 mitogen-activated protein (MAP) kinases, (v) increased NF-kappa B activation and (vi) no significant increase in dark basal keratinocytes. Subsequently, when AD and sanguinarine alkaloid was tested either as complete or stage I or stage II tumor promoter in 7,12-dimethyl benz(a)anthracene (DMBA)-initiated mice, there was enhanced tumor incidence, tumor body burden and higher % of mice with tumors, when AO (0.1 ml) or isolated sanguinarine (1.5 mu mol) was tested as stage II tumor promoter. However, no tumors were found when AO or sanguinarine alkaloid was tested either as complete or stage I tumor promoter. These results indicate that AO/ sanguinarine alkaloid possesses tumor-promoting potential at stage II level involving MAPK/NF-kappa B pathway. (C) 2009 Elsevier Ltd. All rights reserved.