title: Differential effects of superoxide dismutase and superoxide dismutase/catalase mimetics on human breast cancer cells.
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.
authors: Victorian Breast Cancer Research, Invasion and Metastasis Unit, St. Vincent's Institute of Medical Research, 41 Victoria Parade, Fitzroy, VIC, 3065, Australia, Manishashah0513@gmail.com.
authors: Manisha H
authors: MH
authors: Shah
authors: Guei-Sheung
authors: GS
authors: Liu
authors: Erik W
authors: EW
authors: Thompson
authors: Gregory J
authors: GJ
authors: Dusting
authors: Hitesh M
authors: HM
authors: Peshavariya
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D061986:MCF-7 Cells; D008665:Metalloporphyrins / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology*; D012459:Salicylates / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism*
chemical_list: D000975:Antioxidants; C433928:EUK-134; D008665:Metalloporphyrins; C502230:Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin; D016328:NF-kappa B; D009942:Organometallic Compounds; D012459:Salicylates; D013481:Superoxides; D006861:Hydrogen Peroxide