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

Kód výsledku v 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>

Nalezeny alternativní kódy

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

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

<a href="/cs/project/NV17-28231A" target="_blank" >NV17-28231A: Exprese biotransformačních enzymů u primárních nádorů jater</a><br>

Návaznosti

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

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Toxicology

ISSN

0300-483X

e-ISSN

—

Svazek periodika

461

Číslo periodika v rámci svazku

SEP 2021

Stát vydavatele periodika

IE - Irsko

Počet stran výsledku

10

Strana od-do

152897

Kód UT WoS článku

000696272700006

EID výsledku v databázi Scopus

2-s2.0-85113778859