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Caffeine inhibits UV-mediated NF-κB activation in A2058 melanoma cells: an ATM-PKCδ-p38 MAPK-dependent mechanism

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Abstract

Mammalian ultraviolet (UV) radiation response is a gene induction cascade activated by several transcription factors, including NF-κB. Although NF-κB is induced by UV radiation, the signal transduction mechanism remains relatively unclear. In the present study, we show that UV-induced NF-κB activation is mediated by the activation of Ataxia telangiecia mutated (ATM) and protein kinase C (PKC). We also show that caffeine specifically inhibits UV-mediated NF-κB activation, but not TNFα-mediated NF-κB activation. In addition, our study shows that ATM, but not ATM-Rad3-related (ATR) or DNA-dependent protein kinase (DNA-PK) is involved in UV-induced NF-κB activation. Because SB203580 (a p38 MAPK inhibitor), or Calphostin C or rottlerin (PKC inhibitors) was able to inhibit UV-mediated NF-κB activation, we evaluated whether caffeine could inhibit p38 MAPK or PKC activity. Caffeine or rottlerin inhibited UV-induced phosphorylation of p38 MAPK, but not anisomycin-induced phosphorylation of p38 MAPK, suggesting that p38 MAPK is downstream of PKC. Additionally, caffeine could effectively inhibit UV-induced increases in PKC activity. Taken together, our study demonstrates that caffeine is a potent inhibitor of UV-induced NF-κB activation. Additionally, this inhibition occurs due to the inhibitory action of caffeine on ATM and PKC, resulting in the inhibition of p38 MAPK activation.

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Acknowledgments

This study was supported in part by research project grant from the American Cancer Society (KCD) and HL 071558 from the NIH (KCD). The authors also acknowledge the generous contribution of ATR plasmids by Dr Karlene Cimprich at Stanford University.

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  1. Department of Pathology, University of Arkansas for Medical Sciences, 4301 W Markham Street, Slot # 845, Little Rock, AR, 72205, USA

    Dashnamoorthy Ravi, Harish Muniyappa & Kumuda C. Das

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  1. Dashnamoorthy Ravi
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  2. Harish Muniyappa
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  3. Kumuda C. Das
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Correspondence to Kumuda C. Das.

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Ravi, D., Muniyappa, H. & Das, K.C. Caffeine inhibits UV-mediated NF-κB activation in A2058 melanoma cells: an ATM-PKCδ-p38 MAPK-dependent mechanism. Mol Cell Biochem 308, 193–200 (2008). https://doi.org/10.1007/s11010-007-9628-x

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  • DOI: https://doi.org/10.1007/s11010-007-9628-x

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