Chemopreventive properties of aryl hydrocarbon receptor antagonists

描述（由申请人提供）：芳烃受体（AHR）可能在烟草烟雾诱导肺癌的病因学中发挥重要作用，也可能是有效化学预防方法的重要靶点。我们在人肺上皮细胞中进行的初步数据表明，香烟烟雾凝聚物中的成分可以作为AHR激动剂，并且几种膳食类黄酮，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。本研究拟验证的假设是：AHR是膳食黄酮类化合物的重要药理靶点，对烟草烟雾诱导的肺癌具有化学预防作用。具体目的：(1)确定香烟烟气冷凝物激活AHR和细胞转化的程度，黄酮类化合物抑制AHR和细胞转化的程度。(2)在体内确定芹菜素是否抑制香烟烟雾凝聚物诱导的人肺上皮细胞恶性转化。

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.