Deregulation of signaling pathways controlling cell survival and proliferation in cancer cells alters induction of cytochrome P450 family 1 enzymes

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F21%3A00546654" target="_blank" >RIV/68081707:_____/21:00546654 - isvavai.cz</a>

Alternative codes found

RIV/00179906:_____/21:10432646 RIV/00216224:14310/21:00122306

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S0300483X21002201?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0300483X21002201?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.tox.2021.152897" target="_blank" >10.1016/j.tox.2021.152897</a>

Result language

angličtina

Original language name

Deregulation of signaling pathways controlling cell survival and proliferation in cancer cells alters induction of cytochrome P450 family 1 enzymes

Original language description

Cytochrome P450 family 1 (CYP1) enzymes contribute both to metabolism of xenobiotics and to the control of endogenous levels of ligands of the aryl hydrocarbon receptor (AhR). Their activities, similar to other CYPs, can be altered in tumor tissues. Here, we examined a possible role of proliferative/survival pathways signaling, which is often deregulated in tumor cells, and possible links with p300 histone acetyltransferase (a transcriptional co-activator) in the control of CYP1 expression, focusing particularly on CYP1A1. Using cell models derived from human liver, we observed that the induction of CYP1A1 expression, as well as other CYP1 enzymes, was reduced in exponentially growing cells, as compared with their non-dividing counterparts. The siRNAmediated inhibition of proliferation/pro-survival signaling pathway effectors (such as beta-catenin and/or Hippo pathway effectors YAP/TAZ) increased the AhR ligand-induced CYP1A1 mRNA levels in liver HepaRG cells, and/ or in colon carcinoma HCT-116 cells. The activation of proliferative Wnt/beta-catenin signaling in HCT-116 cells reduced both the induction of CYP1 enzymes and the binding of p300 to the promoter of CYP1A1 or CYP1B1 genes. These results seem to indicate that aberrant proliferative signaling in tumor cells could suppress induction of CYP1A1 (or other CYP1 enzymes) via competition for p300 binding. This mechanism could be involved in modulation of the metabolism of both endogenous and exogenous substrates of CYP1A1 (and other CYP1 enzymes), with possible further consequences for alterations of the AhR signaling in tumor cells, or additional functional roles of CYP1 enzymes.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30104 - Pharmacology and pharmacy

Project

<a href="/en/project/NV17-28231A" target="_blank" >NV17-28231A: Expression of biotransformation enzymes in primary liver cancers</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Toxicology

ISSN

0300-483X

e-ISSN

—

Volume of the periodical

461

Issue of the periodical within the volume

SEP 2021

Country of publishing house

IE - IRELAND

Number of pages

10

Pages from-to

152897

UT code for WoS article

000696272700006

EID of the result in the Scopus database

2-s2.0-85113778859