Cytochromes P450: Role in Carcinogenesis and Relevance to Cancers

• 發表在: Current Drug Metabolism
• 主要作者: 2-s2.0-85134797462
• 格式: Review
• 語言: English
• 出版: Bentham Science Publishers 2022
• 在線閱讀: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85134797462&doi=10.2174%2f1389200223666220328143828&partnerID=40&md5=58218880c8e5b2106e85c428d5e93a35

Cancer is a leading cause of mortality globally. Cytochrome P450 (CYP) enzymes play a pivotal role in the biotransformation of both endogenous and exogenous compounds. Various lines of evidence from epidemiological, animal, and clinical studies point to the instrumental role of CYPs in cancer initiation, metastasis, and prevention. Substantial research has found that CYPs are involved in activating different carcinogenic chemicals in the environ-ment, such as polycyclic aromatic hydrocarbons and tobacco-related nitrosamines. Electrophilic intermediates produced from these chemicals can covalently bind to DNA, inducing mutation and cellular transformation that collective-ly result in cancer development. While bioactivation of procarcinogens and promutagens by CYPs has long been established, the role of CYP-derived endobiotics in carcinogenesis has only emerged in recent years. Eicosanoids derived from arachidonic acid via CYP oxidative pathways have been implicated in tumorigenesis, cancer progression and metastasis. The purpose of this review is to update the current state of knowledge about the molecular cancer mechanism involving CYPs with a focus on the biochemical and biotransformation mechanisms in the various CYP-mediated carcinogenesis and the role of CYP-derived reactive metabolites, from both external and endogenous sources, in cancer growth and tumor formation. © 2022 Bentham Science Publishers.