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Green tea polyphenol EGCG suppresses cigarette smoke condensate-induced NF-κB activation in normal human bronchial epithelial cells

Oncogene volume 26, pages 673–682 (2007)Cite this article

Abstract

Cigarette smoke is a powerful inducer of inflammatory responses resulting in disruption of major cellular pathways with transcriptional and genomic alterations driving the cells towards carcinogenesis. Cell culture and animal model studies indicate that (−)-epigallocatechin-3-gallate (EGCG), the major polyphenol present in green tea, possesses potent anti-inflammatory and antiproliferative activity capable of selectively inhibiting cell growth and inducing apoptosis in cancer cells without adversely affecting normal cells. Here, we demonstrate that EGCG pretreatment (20–80 μ M) of normal human bronchial epithelial cells (NHBE) resulted in significant inhibition of cigarette smoke condensate (CSC)-induced cell proliferation. Nuclear factor-κB (NF-κB) controls the transcription of genes involved in immune and inflammatory responses. In most cells, NF-κB prevents apoptosis by mediating cell survival signals. Pretreatment of NHBE cells with EGCG suppressed CSC-induced phosphorylation of IκBα, and activation and nuclear translocation of NF-κB/p65. NHBE cells transfected with a luciferase reporter plasmid containing an NF-κB-inducible promoter sequence showed an increased reporter activity after CSC exposure that was specifically inhibited by EGCG pretreatment. Immunoblot analysis showed that pretreatment of NHBE cells with EGCG resulted in a significant downregulation of NF-κB-regulated proteins cyclin D1, MMP-9, IL-8 and iNOS. EGCG pretreatment further inhibited CSC-induced phosphorylation of ERK1/2, JNK and p38 MAPKs and resulted in a decreased expression of PI3K, AKT and mTOR signaling molecules. Taken together, our data indicate that EGCG can suppress NF-κB activation as well as other pro-survival pathways such as PI3K/AKT/mTOR and MAPKs in NHBE cells, which may contribute to its ability to suppress inflammation, proliferation and angiogenesis induced by cigarette smoke.

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Abbreviations

EGCG:

(−)-epigallocatechin-3-gallate

NHBE:

normal human bronchial epithelial cells

CSC:

cigarette smoke condensate

NF-κB:

nuclear factor-κB

mTOR:

mammalian target of rapamycin

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Acknowledgements

This study was supported by the developmental funds from US Public Health Service Grant 5P30 CA 14520 and also used resources of USPHS grants R01 CA 78809 and R01 CA 101039.

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Authors and Affiliations

  1. Department of Dermatology, University of Wisconsin, Madison, WI, USA

    D N Syed, F Afaq, M-H Kweon, N Hadi, N Bhatia, V S Spiegelman & H Mukhtar

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  1. D N Syed
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  2. F Afaq
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  3. M-H Kweon
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Correspondence to H Mukhtar.

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Syed, D., Afaq, F., Kweon, MH. et al. Green tea polyphenol EGCG suppresses cigarette smoke condensate-induced NF-κB activation in normal human bronchial epithelial cells. Oncogene 26, 673–682 (2007). https://doi.org/10.1038/sj.onc.1209829

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