Areca (betel) nut extract activates mitogen-activated protein kinases and NF-κB in oral keratinocytes
Areca (betel) nut extract activates mitogen-activated protein kinases and NF-κB in oral keratinocytes
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DOI：
10.1002/ijc.21104
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发表时间：
2005-09-10
影响因子：
6.4
通讯作者：
Chang, KW
中科院分区：
文献类型：
--
作者：
Lin, SC;Lu, SY;Chang, KW
槟榔最近被国际癌症研究机构证明是一种致癌物质。然而，槟榔对口腔角质形成细胞的信号传导影响仍不清楚。丝裂原激活蛋白激酶超家族，包括细胞外信号调节激酶 (ERK)、c-Jun N 末端激酶 (JNK) 和 p38，以及转录因子 NF-kappa B，是重要的信号传导元件。我们检查了用成熟槟榔提取物 (ANE) 处理的 OECM-1 和 SAS 口腔角质形成细胞中这些信号通路的激活情况。在这两种细胞中，ANE 处理后 0.5 小时，JNK1 活性迅速增加。在 OECM-1 细胞中，ERK 在 0.5-2 小时内被深度激活。在这 2 个细胞中注意到对比的 p38 活性。在这两种细胞中，ANE 还以双相方式激活 NF-κ B 通路，特别是对于 SAS 细胞。 NF-kappa B 在 0.5-1 小时时被激活约 2 至 4 倍，并且在 1 小时和 6 小时之间存在活性稳定或轻微下降。随后，出现了另一个更高的 NF-κ B 活性。这伴随着两种细胞中胞浆 I kappa B α 的快速降解以及核 NF-kappa B 的增加。 ANE 治疗不会激活表皮生长因子受体信号系统，但阻断 NF-κ B 激活可抑制 OECM-1 中 ANE 调节的 COX-2 上调。这项研究发现，ANE 影响口腔角质细胞中的交互信号系统，这可能是槟榔的发病基础。 (c) 2005 年 Wiley-Liss, Inc.
Areca (betel) was recently proved a carcinogenic substance by the International Agency for Research on Cancer. However, the Signaling impact of areca in oral keratinocyte is still obscure. Mitogen-activated protein kinase superfamilies, including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinases (JNK) and p38, together with transcription factor NF-kappa B, are important signaling elements. We examined the activation of these signaling pathways in OECM-1 and SAS oral keratinocytes, treated with ripe areca nut extract (ANE). In both cells, a rapid increase in JNK1 activity at 0.5 hr was noted following treatment of ANE. ERK was profoundly activated during 0.5-2 hr in OECM-1 cells. Contrasting p38 activity was noted in these 2 cells. In both cells, ANE also activated NF-kappa B pathway in a biphasic manner, particularly for SAS cells. NF-kappa B was activated by similar to 2- to 4-fold at 0.5-1 hr and a plateau or slight decrease of activity existed between I and 6 hr. Later, another higher episode of NF-kappa B activity was raised. This was accompanied with the rapid degradation in cytosolic I kappa B alpha as well as an increase of nuclear NF-kappa B in both cells. ANE treatment did not activate epidermal growth factor receptor signaling system, but blockage of NF-kappa B activation rendered the suppression of ANE-modulated COX-2 upregulation in OECM-1. This study identified that ANE affected interactive signaling systems in oral keratonocytes that could be the pathogenetic basis for areca. (c) 2005 Wiley-Liss, Inc.