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NAG-1 up-regulation mediated by EGR-1 and p53 is critical for quercetin-induced apoptosis in HCT116 colon carcinoma cells

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Abstract

Quercetin, a flavonoid molecule ubiquitously present in nature, has multiple effects on cancer cells, including the inhibition of cell proliferation and migration. However, the responsible molecular mechanisms are not fully understood. We found that quercetin induces the expression of NAG-1 (Non-steroidal anti-inflammatory drug activated gene-1), a TGF-β superfamily protein, during quercetin-induced apoptosis of HCT116 human colon carcinoma cells. Reporter assays using the luciferase constructs containing NAG-1 promoter region demonstrate that early growth response-1 (EGR-1) and p53 are required for quercetin-mediated activation of the NAG-1 promoter. Overexpression of NAG-1 enhanced the apoptotic effect of quercetin, but suppression of quercetin-induced NAG-1 expression by NAG-1 siRNA attenuated quercetin-induced apoptosis in HCT116 cells. Taken together, the present study demonstrates for the first time that quercetin induces apoptosis via NAG-1, providing a mechanistic basis for the apoptotic effect of quercetin in colon carcinoma cells.

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Authors and Affiliations

  1. Department of Immunology, School of Medicine, Keimyung University, 194 DongSan-Dong, Taegu, 700–712, Korea

    J. H. Lim, J.-W. Park & T. K. Kwon

  2. Department of Molecular Biology, College of Natural Science, Pusan National University, Korea

    D. S. Min

  3. Department of Life Science, Daejin University, Pochon-gun, Kyeonggido, Korea

    J.-S. Chang

  4. Division of Molecular & Life Science, College of Science & Technology, Hanyang University, Ansan, Korea

    Y. H. Lee

  5. Department of Genetic Engineering, College of Natural Sciences, Kyungpook National University, Taegu, Korea

    J. H. Lim & Y. B. Park

  6. Institute for Medical Science, School of Medicine, Ajou University, Suwon, Korea

    K. S. Choi

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  1. J. H. Lim
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Correspondence to T. K. Kwon.

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Lim, J.H., Park, JW., Min, D.S. et al. NAG-1 up-regulation mediated by EGR-1 and p53 is critical for quercetin-induced apoptosis in HCT116 colon carcinoma cells. Apoptosis 12, 411–421 (2007). https://doi.org/10.1007/s10495-006-0576-9

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  • DOI: https://doi.org/10.1007/s10495-006-0576-9

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