Carcinogenesis, Vol. 20, No. 11, 2137-2142,
November 1999
© 1999 Oxford University Press
Molecular Epidemiology And Cancer Prevention |
Inhibitory effects of deferoxamine on UVB-induced AP-1 transactivation
Department of Radiation Oncology, The University of Arizona Health Sciences Center, Tucson, AZ 85724, USA
Production of reactive oxygen species (ROS) by iron can contribute directly to DNA and protein damage and may contribute to cell signaling and proliferation. We have examined the effects of the iron(III) chelator deferroxamine (DFO) and iron (FeCl3) on UVB (290–320 nm)-induced activator protein 1 (AP-1) signaling. The ability of DFO to inhibit UVB-induced AP-1 transactivation was tested in a human keratinocyte cell line stably transfected with a luciferase reporter driven by a single AP-1 element. DFO treatment 24 h prior to UVB irradiation reduced UVB-induced AP-1 transactivation by ~80%, with the effect of DFO diminishing as pre-treatment time was shortened. Treatment with FeCl3 a minimum of 6 h prior to UVB potentiated the UVB induction of AP-1 transactivation by 2–3-fold. DFO was able to ablate both the UVB induction of AP-1 transactivation as well as the potentiation by FeCl3. The antioxidants Trolox and N-acetyl cysteine were both able to inhibit UVB-induced AP-1 transactivation and Trolox was able to inhibit the potentiation of UVB-induced AP-1 by FeCl3. These results indicate that UVB-induced AP-1 activation may be in part due to oxidant effects of UVB and intercellular iron.
Abbreviations: AP-1, activator protein 1; DFO, deferoxamine; DMEM, Dulbecco's modified Eagle's medium; EGTA, ethylene glycol tetraacetic acid; HCL14, HaCaT cells containing AP-1 regulated luciferase reporter gene; NAC, N-acetyl cysteine; RLU, relative light units; ROS, reactive oxygen species; Trolox-Me, Trolox methyl ether.
1 To whom correspondence should be addressed Email: bowden{at}azcc.arizona.edu
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