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Current Drug Metabolism

Editor-in-Chief

ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Review Article

Cytochromes P450: Role in Carcinogenesis and Relevance to Cancers

Author(s): A’edah Abu-Bakar, Boon Hooi Tan, Hasseri Halim, Salfarina Ramli, Yan Pan and Chin Eng Ong*

Volume 23, Issue 5, 2022

Published on: 08 June, 2022

Page: [355 - 373] Pages: 19

DOI: 10.2174/1389200223666220328143828

Price: $65

Abstract

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 environment, 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 collectively 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.

Keywords: Cytochrome P450, cancer, carcinogenesis, carcinogen, eicosanoid, drug metabolism, DNA adduct.

Graphical Abstract
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