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Differential effects of superoxide dismutase and superoxide dismutase/catalase mimetics on human breast cancer cells

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Abstract

Reactive oxygen species (ROS) such as superoxide and hydrogen peroxide (H2O2) have been implicated in development and progression of breast cancer. In the present study, we have evaluated the effects of the superoxide dismutase (SOD) mimetic MnTmPyP and the SOD/catalase mimetic EUK 134 on superoxide and H2O2 formation as well as proliferation, adhesion, and migration of MCF-7 and MDA-MB-231 cells. Superoxide and H2O2 production was examined using dihydroethidium and Amplex red assays, respectively. Cell viability and adhesion were measured using a tetrazolium-based MTT assay. Cell proliferation was determined using trypan blue assay. Cell cycle progression was analyzed using flow cytometry. Clonal expansion of a single cell was performed using a colony formation assay. Cell migration was measured using transwell migration assay. Dual luciferase assay was used to determine NF-κB reporter activity. EUK 134 effectively reduced both superoxide and H2O2, whereas MnTmPyP removed superoxide but enhanced H2O2 formation. EUK 134 effectively attenuated viability, proliferation, clonal expansion, adhesion, and migration of MCF-7 and MDA-MB-231 cells. In contrast, MnTmPyP only reduced clonal expansion of MCF-7 and MDA-MB-231 cells but had no effect on adhesion and cell cycle progression. Tumor necrosis factor-alpha-induced NF-κB activity was reduced by EUK 134, whereas MnTmPyP enhanced this activity. These data indicate that the SOD mimetic MnTmPyP and the SOD/catalase mimetic EUK 134 exert differential effects on breast cancer cell growth. Inhibition of H2O2 signaling using EUK 134-like compound might be a promising approach to breast cancer therapy.

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Abbreviations

EUK 134:

Eukaration-134; chloro[[2,2′-[1,2-ethanediylbis[(nitrilo-κN)methylidyne]]bis[6-methoxyphenolato-κO]]]-manganese

H2O2 :

Hydrogen peroxide

HMEC:

Human dermal microvascular endothelial cells

MnTmPyP:

Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride

NF-κB:

Nuclear factor kappa B

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

TNFα:

Tumor necrosis factor-alpha

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Acknowledgments

MHS was supported by postdoctoral Fellowship (KG080837) from the Susan G. Komen Foundation for the Cure, USA. GJD is the recipient of an National Health and Medical Research Council Research Fellowship (#1003113). Authors are thankful to Dr. Rachana Sainger for her extensive reading and suggestions for this manuscript. The Centre for Eye Research Australia, St. Vincent’s Institute of Medical Research and O’Brien Institute acknowledge the Victorian State Government’s Department of Innovation, Industry and Regional Development’s Operational Infrastructure Support Program.

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Authors and Affiliations

  1. Victorian Breast Cancer Research, Invasion and Metastasis Unit, St. Vincent’s Institute of Medical Research, 41 Victoria Parade, Fitzroy, VIC, 3065, Australia

    Manisha H. Shah & Erik W. Thompson

  2. Department of Ophthalmology, Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, 1/32 Gisborne Street, East Melbourne, VIC, 3002, Australia

    Guei-Sheung Liu, Gregory J. Dusting & Hitesh M. Peshavariya

  3. O’Brien Institute, Fitzroy, VIC, 3065, Australia

    Guei-Sheung Liu, Gregory J. Dusting & Hitesh M. Peshavariya

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  1. Manisha H. Shah
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Correspondence to Hitesh M. Peshavariya.

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Shah, M.H., Liu, GS., Thompson, E.W. et al. Differential effects of superoxide dismutase and superoxide dismutase/catalase mimetics on human breast cancer cells. Breast Cancer Res Treat 150, 523–534 (2015). https://doi.org/10.1007/s10549-015-3329-z

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