The activation of procarcinogens by CYP1A1/1B1 and related chemopreventive agents: A review.

The activation of procarcinogens by CYP1A1/1B1 and related chemopreventive agents: A review.
Curr Cancer Drug Targets. 2020 Oct 06;:
Authors: Li Y, Cui J, Jia J
Abstract
CYP1A1 and CYP1B1 are extrahepatic P450 family members involved in the metabolism of procarcinogens, such as PAHs, heterocyclic amines and halogen-containing organic compounds. CYP1A1/1B1 also participate in the metabolism of endogenous 17-β-estradiol, producing estradiol hydroquinones which are the intermediates of carcinogenic semiquinones and quinones. CYP1A1 and CYP1B1 proteins share approximately half amino acid sequence identity but differ in crystal structures. As a result, CYP1A1 and CYP1B1 have different substrate specificity to chemical procarcinogens. This review will introduce the general molecular biology knowledge of CYP1A1/1B1 and the metabolic processes of procarcinogens regulated by these two enzymes. Over the last four decades, a variety of natural products and synthetic compounds which interact with CYP1A1/1B1 have been identified as effective chemo-preventive agents against chemical carcinogenesis. These compounds are mainly classified as, indirect or direct CYP1A1/1B1 inhibitors based on their distinct mechanisms. Indirect CYP1A1/1B1 inhibitors generally impede the transcription and translation of CYP1A1/1B1 genes or interfere the translocation of aryl hydrocarbon receptor (AHR) from the cytosolic domain to the nucleus. On the other hand, direct...

Source: Current Cancer Drug Targets - October 6, 2020 Category: Cancer & Oncology Authors: Li Y, Cui J, Jia J Tags: Curr Cancer Drug Targets Source Type: research