Zhu Wei, Xu Jing, Ge Yangyang, Cao Han, Ge Xin, Luo Judong, Xue Jiao, Yang Hongying, Zhang Shuyu, Cao Jianping
School of Radiation Medicine and Protection and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions and School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, No. 199 Ren'ai Road, Suzhou 215123, China.
Department of Radiotherapy, Changzhou Tumor Hospital, Soochow University, Changzhou, 213001, China.
J Radiat Res. 2014 Nov;55(6):1056-65. doi: 10.1093/jrr/rru047. Epub 2014 Jun 26.
Epigallocatechin-3-gallate (EGCG), the major polyphenolic constituent of green tea, is a potent antioxidant and free radical scavenger that may have therapeutic applications for the treatment of many disorders. Radiation therapy is widely used for the treatment of various types of cancers; however, radiation-induced skin injury remains a serious concern. EGCG has not yet been reported as protecting skin cells against ionizing radiation. In the present study, we investigated whether EGCG confers cytoprotection against ionizing radiation. We found that, compared with the control, pretreatment with EGCG significantly enhanced the viability of human skin cells that were irradiated with X-rays, and decreased apoptosis induced by X-ray irradiation. Mito-Tracker assay showed that EGCG suppressed the damage to mitochondria induced by ionizing radiation via upregulation of SOD2. Reactive oxygen species (ROS) in HaCaT cells were significantly reduced when pretreated with EGCG before irradiation. Radiation-induced γH2AX foci, which are representative of DNA double-strand breaks, were decreased by pretreatment with EGCG. Furthermore, EGCG induced the expression of the cytoprotective molecule heme oxygenase-1 (HO-1) in a dose-dependent manner via transcriptional activation. HO-1 knockdown or treatment with the HO-1 inhibitor tin protoporphyrin (SnPPIX) reversed the protective role of EGCG, indicating an important role for HO-1. These results suggest that EGCG offers a new strategy for protecting skin against ionizing radiation.
表没食子儿茶素-3-没食子酸酯(EGCG)是绿茶中的主要多酚成分,是一种有效的抗氧化剂和自由基清除剂,可能对多种疾病的治疗具有治疗应用价值。放射治疗广泛用于治疗各种类型的癌症;然而,辐射引起的皮肤损伤仍然是一个严重问题。尚未有报道称EGCG能保护皮肤细胞免受电离辐射。在本研究中,我们调查了EGCG是否赋予细胞对电离辐射的保护作用。我们发现,与对照组相比,用EGCG预处理可显著提高经X射线照射的人皮肤细胞的活力,并减少X射线照射诱导的细胞凋亡。线粒体追踪分析表明,EGCG通过上调SOD2抑制电离辐射诱导的线粒体损伤。在照射前用EGCG预处理时,HaCaT细胞中的活性氧(ROS)显著减少。代表DNA双链断裂的辐射诱导的γH2AX焦点通过EGCG预处理而减少。此外,EGCG通过转录激活以剂量依赖性方式诱导细胞保护分子血红素加氧酶-1(HO-1)的表达。HO-1基因敲低或用HO-1抑制剂锡原卟啉(SnPPIX)处理可逆转EGCG的保护作用,表明HO-1具有重要作用。这些结果表明,EGCG为保护皮肤免受电离辐射提供了一种新策略。