Inhibitory effect of glycolic acid on ultraviolet B-induced c-fos expression, AP-1 activation and p53-p21 response in a human keratinocyte cell line
Inhibitory effect of glycolic acid on ultraviolet B-induced c-fos expression, AP-1 activation and p53-p21 response in a human keratinocyte cell line
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DOI：
10.1016/s0304-3835(02)00283-5
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发表时间：
2002-12-05
期刊：
影响因子：
9.7
通讯作者：
Hong, JT
中科院分区：
文献类型：
--
作者：
Ahn, KS;Park, KS;Hong, JT
乙醇酸是一种源自水果和牛奶糖的α-羟基酸，由于已知其具有光保护和抗炎作用，以及在紫外线照射的皮肤中具有抗氧化作用，因此通常用作化妆品成分。然而，很少有人知道的功能作用，乙醇酸对紫外线诱导的皮肤肿瘤发生。我们以前发现乙醇酸抑制紫外线诱导的无毛小鼠皮肤肿瘤的发展。本研究旨在探讨羟基乙酸对紫外线诱导的皮肤肿瘤生长的抗肿瘤促进机制。检测乙醇酸抑制UVB诱导的细胞毒性、细胞凋亡和凋亡调节基因（p53和p21）表达的能力。我们还研究了乙醇酸是否可以抑制UVB诱导的细胞周期，c-fos的表达和转录因子AP-1的激活在培养的永生化的人角质形成细胞HaCaT细胞的交替。乙醇酸处理减弱UVB诱导的细胞毒性以及凋亡。乙醇酸还能抑制UVB诱导的c-fos基因表达和转录因子AP-1的激活，抑制凋亡调控基因p53和p21的mRNA水平。结果提示，乙醇酸可能通过抑制p53-p21反应通路、抑制c-fos表达和激活AP-1，阻断UVB诱导的细胞凋亡和细胞毒作用，从而抑制UVB诱导的皮肤肿瘤的发生。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
Glycolic acid, an alpha-hydroxy acid derived from fruit and milk sugars, has been commonly used as a cosmetic ingredient since it was known to have photo-protective and anti-inflammatory effects, and anti-oxidant effect in UV-irradiated skin. However, little has been known about the functional role of glycolic acid on UV-induced skin tumorigenesis. We previously found that glycolic acid inhibited UV-induced skin tumor development in hairless mouse. In this study we investigated antitumor promoting mechanism of glycolic acid on the UV-induced skin tumor development. The ability of glycolic acid to inhibit the UVB-induced cytotoxicity, apoptosis and expression of apoptosis-regulatory genes (p53 and p21) was examined. We also investigated whether glycolic acid could inhibit UVB-induced alternation of cell cycle, c-fos expression and activation of transcription factor AP-1 in cultured immortalized human keratinocyte HaCaT cells. Glycolic acid treatment attenuated the UVB-induced cell cytotoxicity as well as apoptosis. Glycolic acid also inhibited the UVB-induced expression of c-fos and the activation of transcription factor AP-1, and inhibited mRNA levels of apoptosis-regulatory gene (p53 and p21). These results suggest that glycolic acid may exert the inhibitory effect on the UVB-induced skin tumor development by blocking the UVB-induced of apoptosis and cytotoxicity through inhibition of c-fos expression and activation of AP-1 in addition to the inhibition of p53-p21 response pathway. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.