Chemopreventive properties of aryl hydrocarbon receptor antagonists

University Of Kentucky, Lexington KY

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Abstract

[unreadable] DESCRIPTION (provided by applicant): The aryl hydrocarbon receptor (AHR) may play in important role in the etiology of tobacco smoke induced lung cancer and may also be an important target for effective chemopreventive approaches. Our initial data performed in human lung epithelial cells indicates that constituents present in cigarette smoke condensate can act as AHR agonists and that several dietary flavonoids, in particular, apigenin, emodin and kaempferol appear to act as effective AHR antagonists. The hypothesis to be tested in this proposal is that the AHR is an important pharmacological target of dietary flavonoids that will be effective for chemoprevention of tobacco smoke induced lung cancer. Specific Aims: (1) Determine the extent to which cigarette smoke condensate activates and flavonoids inhibit the AHR and cell transformation. (2) Determine whether apigenin inhibits cigarette smoke condensate-induced malignant transformation of human lung epithelial cells in vivo. [unreadable] [unreadable] [unreadable]