儿茶酚黄酮是含邻苯二酚结构的一类黄酮，流行病学研究显示，儿茶酚黄酮摄入量与肿瘤风险降低存在相关性，儿茶酚黄酮有潜力开发成预防和治疗肿瘤的药物。目前，儿茶酚黄酮的体内代谢过程和抗肿瘤活性分子形式尚未清楚，阻碍了儿茶酚黄酮的抗肿瘤开发利用。本课题组前期研究发现，儿茶酚氧位甲基转移酶（COMT）识别邻苯二酚结构，可介导儿茶酚黄酮的甲基化代谢；而CYP1A2和CYP3A4（CYP1A2/3A4）可介导儿茶酚黄酮甲基化产物的去甲基代谢。本课题拟研究儿茶酚黄酮经COMT介导的甲基化代谢和进一步经CYP1A2/3A4介导的去甲基化代谢，一方面，阐明COMT介导的甲基化代谢在儿茶酚黄酮体内处置及抗肿瘤活性中的作用，另一方面，阐明CYP1A2/3A4代谢激活儿茶酚黄酮甲基化产物的抗肿瘤作用机制。本研究结果将完善儿茶酚黄酮的体内代谢图谱和抗肿瘤作用机制信息，为儿茶酚黄酮抗肿瘤药物研发提供参考依据。

Epidemiologic studies suggested that intake of catecholic flavonoids was associated with reduced cancer risk. Catecholic flavonoids were potential to be developed as drugs for cancer prevention and treatment. Catechol-O-methyl transferase (COMT ) could methylate the catecholic ring at hydroxyls; however, there was lack of study about the methylation of catecholic flavonoids，especially about the structure identification and activity study of the methylated catecholic flavonoids. In addition, methylated metabolites might be activated by CYP1A2 and CYP3A4 (CYP1A2/3A4) with demethylation in vivo, which was unclear with methylated catecholic flavonoids. Therefore, our study is aimed to clarify the role of COMT and CYP1A2/3A4 in the disposition of catecholic flavonoids and its association with their anti-tumor activities. This results will enhance the knowledge of pharmacokinetics of catecholic flavonoids in vivo and help to explain their anti-tumor activities and anti-tumor mechanism in vivo, which all provides useful information for development of drugs for cancer prevention and treatment from catecholic flavonoids.