Chemopreventive properties of aryl hydrocarbon receptor antagonists

描述（由申请人提供）： 芳烃受体（AHR）可能在吸烟诱发肺癌的发病机制中起重要作用，也可能是有效化学预防的重要靶点。我们在人肺上皮细胞中进行的初步数据表明，香烟烟雾冷凝物中存在的成分可以作为AHR激动剂，并且几种膳食黄酮类化合物，特别是芹菜素，大黄素和山奈酚似乎可以作为有效的AHR拮抗剂。在该提议中待检验的假设是，AHR是膳食类黄酮的重要药理学靶点，其将有效用于烟草烟雾诱导的肺癌的化学预防。具体目的：（1）确定香烟烟雾冷凝物激活和黄酮类化合物抑制AHR和细胞转化的程度。(2)确定芹菜素是否抑制香烟烟雾冷凝物诱导的人肺上皮细胞的恶性转化。

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.