College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea.
Arch Pharm Res. 2021 Jan;44(1):63-83. doi: 10.1007/s12272-021-01306-w. Epub 2021 Jan 23.
Human cytochrome P450 enzymes (CYPs) play a critical role in various biological processes and human diseases. CYP1 family members, including CYP1A1, CYP1A2, and CYP1B1, are induced by aryl hydrocarbon receptors (AhRs). The binding of ligands such as polycyclic aromatic hydrocarbons activates the AhRs, which are involved in the metabolism (including oxidation) of various endogenous or exogenous substrates. The ligands that induce CYP1 expression are reported to be carcinogenic xenobiotics. Hence, CYP1 enzymes are correlated with the pathogenesis of cancers. Various endogenous substrates are involved in the metabolism of steroid hormones, eicosanoids, and other biological molecules that mediate the pathogenesis of several human diseases. Additionally, CYP1s metabolize and activate/inactivate therapeutic drugs, especially, anti-cancer agents. As the metabolism of drugs determines their therapeutic efficacy, CYP1s can determine the susceptibility of patients to some drugs. Thus, understanding the role of CYP1s in diseases and establishing novel and efficient therapeutic strategies based on CYP1s have piqued the interest of the scientific community.
人类细胞色素 P450 酶(CYPs)在各种生物过程和人类疾病中起着关键作用。CYP1 家族成员,包括 CYP1A1、CYP1A2 和 CYP1B1,受芳香烃受体(AhR)诱导。配体(如多环芳烃)与 AhR 结合,AhR 参与各种内源性或外源性底物的代谢(包括氧化)。据报道,诱导 CYP1 表达的配体是致癌性的外源性化学物质。因此,CYP1 酶与癌症的发病机制有关。各种内源性底物参与甾体激素、类花生酸和其他介导几种人类疾病发病机制的生物分子的代谢。此外,CYP1 代谢并激活/失活治疗药物,特别是抗癌药物。由于药物的代谢决定了其治疗效果,CYP1 可以决定患者对某些药物的敏感性。因此,了解 CYP1 在疾病中的作用,并基于 CYP1 建立新的有效治疗策略,引起了科学界的兴趣。