The oxygen radicals involved in the toxicity induced by parthenolide in MDA-MB-231 cells

被引:29
作者
Carlisi, Daniela [1 ]
D'Anneo, Antonella [2 ]
Martinez, Roberta [1 ]
Emanuele, Sonia [1 ]
Buttitta, Giuseppina [1 ]
Di Fiore, Riccardo [2 ]
Vento, Renza [2 ,3 ]
Tesoriere, Giovanni [2 ,3 ]
Lauricella, Marianna [1 ]
机构
[1] Univ Palermo, Dept Expt Biomed & Clin Neurosci, Biochem Lab, I-90127 Palermo, Italy
[2] Univ Palermo, Dept Biol Chem & Pharmaceut Sci & Technol, Biochem Lab, I-90127 Palermo, Italy
[3] Temple Univ, Coll Sci & Technol, Sbarro Inst Canc Res & Mol Med, Philadelphia, PA 19122 USA
关键词
parthenolide; oxygen radicals; NADPH oxidase; breast cancer cells; SUPEROXIDE ANION; BREAST-CANCER; APOPTOSIS; RECEPTOR; PATHWAY;
D O I
10.3892/or.2014.3212
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
It has been shown that the sesquiterpene lactone parthenolide lowers the viability of MDA-MB-231 breast cancer cells, in correlation with oxidative stress. The present report examined the different radical species produced during parthenolide treatment and their possible role in the toxicity caused by the drug. Time course experiments showed that in the first phase of treatment (0-8 h), and in particular in the first 3 h, parthenolide induced dichlorofluorescein (DCF) signal in a large percentage of cells, while dihydroethidium (DHE) signal was not stimulated. Since the effect on DCF signal was suppressed by apocynin and diphenyleneiodonium (DPI), two inhibitors of NADPH oxidase (NOX), we suggest that parthenolide rapidly stimulated NOX activity with production of superoxide anion (O-2(center dot-)), which was converted by superoxide dismutase 1 (SOD1) into hydrogen peroxide (H2O2). In the second phase of treatment (8-16 h), parthenolide increased the number of positive cells to DHE signal. Since this event was not prevented by apocynin and DPI and was associated with positivity of cells to MitoSox Red, a fluorochrome used to detect mitochondrial production of O-2(center dot-), we suggest that parthenolide induced production of O-2(center dot-) at the mitochondrial level independently by NOX activity in the second phase of treatment. Finally, in this phase, most cells became positive to hydroxyphenyl fluorescein (HPF) signal, a fluorescent probe to detect highly reactive oxygen species (hROS), such as hydroxyl radical and peroxynitrite. Therefore, parthenolide between 8-16 h of treatment induced generation of O-2(center dot-) and hROS, in close correlation with a marked reduction in cell viability.
引用
收藏
页码:167 / 172
页数:6
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