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

Carlisi,Daniela; D'Anneo,Antonella; Martinez,Roberta; Emanuele,Sonia; Buttitta,Giuseppina; Di Fiore,Riccardo; Vento,Renza; Tesoriere,Giovanni; Lauricella,Marianna

doi:10.3892/or.2014.3212

July-2014 Volume 32 Issue 1

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July-2014 Volume 32 Issue 1

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Article

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

Authors:
- Daniela Carlisi
- Antonella D'Anneo
- Roberta Martinez
- Sonia Emanuele
- Giuseppina Buttitta
- Riccardo Di Fiore
- Renza Vento
- Giovanni Tesoriere
- Marianna Lauricella
View Affiliations / Copyright

Affiliations: Laboratory of Biochemistry, Department of Experimental Biomedicine and Clinical Neurosciences, Polyclinic, University of Palermo, 90127 Palermo, Italy, Laboratory of Biochemistry, Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Polyclinic, University of Palermo, 90127 Palermo, Italy
Pages: 167-172
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Published online on: May 23, 2014

https://doi.org/10.3892/or.2014.3212
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Abstract

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 (O2•-), 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 O2•-, we suggest that parthenolide induced production of O2•- 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 O2•- and hROS, in close correlation with a marked reduction in cell viability.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

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