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金纳米粒子增强 5-氨基酮戊酸诱导的两种癌细胞系的氧化应激。

Enhancement of 5-Aminolevulinic acid-induced oxidative stress on two cancer cell lines by gold nanoparticles.

机构信息

Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1002, USA.

出版信息

Free Radic Res. 2009 Dec;43(12):1214-24. doi: 10.3109/10715760903271249.

Abstract

5-Aminolevulinic acid (5-ALA) and its methyl ester (5-ALA-Me) at mM concentration levels induce oxidative stress via the production of reactive oxygen species (ROS). Human cancer cell lines (MCF-7 and HepG2) incubated in the dark in the simultaneous presence of 5.0 mM or more 5-ALA or 5-ALA-Me (for MCF-7) and 7 microg/mL of 15 nm citrate capped gold nanoparticles (AuNPs) were damaged more seriously compared to those in the presence of the levulinic acid alone. Damage is visible in electron micrographs which reveal similar morphology both in the presence or absence of AuNPs. Cytotoxicity was observed irrespective of the presence of serum and medium. Production of ROS in cell free samples containing 5-ALA-Me was monitored by EPR as the DMPO-OH spin adduct and also showed a catalytic effect of AuNPs. Both SOD and CAT inhibited the production of ROS and also reduced cytotoxicity in the cell samples. These observations can be explained by initial attack on the cell membrane by ROS produced in the medium outside the cell and provide insight into possible uses of 5-ALA in cancer chemotherapy.

摘要

5-氨基酮戊酸(5-ALA)及其甲酯(5-ALA-Me)在毫摩尔浓度水平下通过产生活性氧(ROS)诱导氧化应激。在黑暗中孵育的人癌细胞系(MCF-7 和 HepG2),同时存在 5.0 mM 或更高浓度的 5-ALA 或 5-ALA-Me(用于 MCF-7)和 7 微克/毫升的 15nm 柠檬酸封端金纳米粒子(AuNPs),与单独存在亮氨酸酸相比,损伤更为严重。电子显微镜照片显示,无论是否存在 AuNPs,损伤都是可见的。在含有 5-ALA-Me 的无细胞样品中,通过 EPR 监测到 ROS 的产生,其作为 DMPO-OH 自旋加合物,并且还显示 AuNPs 的催化作用。SOD 和 CAT 均抑制 ROS 的产生,并降低细胞样品中的细胞毒性。这些观察结果可以通过细胞外介质中产生的 ROS 对细胞膜的初始攻击来解释,并为 5-ALA 在癌症化疗中的可能用途提供了见解。

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