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

被引:41
作者
Ito, Shinji [1 ]
Miyoshi, Norio [2 ]
Degraff, William G. [1 ]
Nagashima, Kunio [3 ]
Kirschenbaum, Louis J. [4 ]
Riesz, Peter [1 ]
机构
[1] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
[2] Univ Fukui, Fac Med, Dept Pathol Sci, Div Tumor Pathol, Matsuoka, Fukui 9101193, Japan
[3] NCI, Electron Microscope Lab, SAIC Frederick, NIH, Frederick, MD 21702 USA
[4] Univ Rhode Isl, Dept Chem, Kingston, RI 02881 USA
基金
美国国家卫生研究院;
关键词
Gold nanoparticles; 5-Aminolevulinic acid; cytotoxicity; reactive oxygen species; DELTA-AMINOLEVULINIC-ACID; PHOTODYNAMIC THERAPY; FREE-RADICALS; CYTOTOXICITY; AUTOXIDATION; SIZE; CONNECTIONS; GENERATION; ESTERS;
D O I
10.3109/10715760903271249
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
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 mu g/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.
引用
收藏
页码:1214 / 1224
页数:11
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