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Protection and Sensitization of Normal and Malignant Cells by a Naturally-Occurring Compound in a Model of Photochemical Damage

机译:在光化学损伤模型中天然存在的化合物对正常和恶性细胞的保护和敏化作用

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摘要

Certain phytonutrients are known to confer protection and immunosuppression against radiation insults. Radiation-induced reactive oxygen species (ROS) can either lead to the destruction of normal tissue cells, or induce tumor radioresistance by activating ROS scavenging proteins. To identify whether the triterpene phytonutrient, ursolic acid, reduces radiation-induced damage in normal cells and promotes the apoptosis of malignant cells, we investigated the biologic mechanisms and effect of radiation-cell interaction with or without treatment with ursolic acid in human skin melanoma cells (ATCC CRL-11147~(™)) and transformed human retinal pigment epithelial (hTERT-RPE) cells. UV-VIS light was employed to investigate the efficacy of ursolic acid in altering cellular viability by modulations of p53 and NF-kB p65 signaling. Cell response was investigated by changes in proliferative activity and free radical generation assessed by 2',7'-dichlorofluorescin liquid chromatography. Ursolic acid pretreatment strongly increased the level of p53 and decreased the level of phosphorylated p65 leading to enhanced cell death of skin melanoma cells in response to UV-VIS exposure. In contrast, ursolic acid appeared to down-regulate p53 levels without disturbing NF-kB activation along with an increase of oxidative stress in hTERT-RPE cells. These findings indicate that ursolic acid may beneficially increase the radiosensitivity of tumor cells while potentiating a photoprotective effect on benign cells through differential effects on the NF-kB and p53 signaling pathways.
机译:已知某些植物营养素可针对辐射损伤提供保护和免疫抑制。辐射诱导的活性氧(ROS)可以导致正常组织细胞的破坏,或者通过激活ROS清除蛋白来诱导肿瘤的抗辐射性。为了确定三萜植物营养素,熊果酸是否能减少辐射对正常细胞的损害并促进恶性细胞的凋亡,我们研究了在人类皮肤黑素瘤细胞中使用或不使用熊果酸治疗的辐射细胞相互作用的生物学机制和作用。 (ATCC CRL-11147〜(TM))和转化的人视网膜色素上皮细胞(hTERT-RPE)。 UV-VIS光用于研究熊果酸通过调节p53和NF-kB p65信号传导改变细胞生存力的功效。通过2',7'-二氯荧光素液相色谱评估增殖活性和自由基产生的变化来研究细胞反应。熊果酸预处理强烈增加了p53的水平,降低了磷酸化的p65的水平,从而导致皮肤黑素瘤细胞对UV-VIS的暴露增加了细胞死亡。相反,熊果酸似乎在不干扰NF-kB活化以及hTERT-RPE细胞中氧化应激增加的情况下下调p53水平。这些发现表明,熊果酸可以通过对NF-κB和p53信号通路的不同作用来增强肿瘤细胞的放射敏感性,同时增强对良性细胞的光保护作用。

著录项

  • 来源
    《Optical interactions with tissue and cells XXIII》|2012年|p.82211M.1-82211M.13|共13页
  • 会议地点 San Francisco CA(US)
  • 作者单位

    Dept. of Radiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, ~*USA;

    Dept. of Ophthalmology, University of Texas Health Science Center at San Antonio, San Antonio, TX, ~*USA;

    Dept. of Ophthalmology, University of Texas Health Science Center at San Antonio, San Antonio, TX, ~*USA,Center for Biomedical Neuroscience University of Texas Health Science Center at San Antonio, San Antonio, TX, ~*USA;

  • 会议组织
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 医用物理学;
  • 关键词

    ursolic acid; p53; NF-kB; radiation; sensitization;

    机译:熊果酸p53; NF-kB;辐射;敏化;

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