Aryl Hydrocarbon Receptor-Dependent Metabolism Plays a
Significant Role in Estrogen-Like Effects of Polycyclic
Aromatic Hydrocarbons on Cell Proliferation

J 2018

Aryl Hydrocarbon Receptor-Dependent Metabolism Plays a Significant Role in Estrogen-Like Effects of Polycyclic Aromatic Hydrocarbons on Cell Proliferation

HYZDALOVA, M., Jakub PIVNIČKA, Ondřej ZAPLETAL, G. VAZQUEZ-GOMEZ, J. MATTHEWS et. al.

Základní údaje

Originální název

Aryl Hydrocarbon Receptor-Dependent Metabolism Plays a Significant Role in Estrogen-Like Effects of Polycyclic Aromatic Hydrocarbons on Cell Proliferation

Autoři

HYZDALOVA, M., Jakub PIVNIČKA (203 Česká republika, domácí), Ondřej ZAPLETAL (203 Česká republika, domácí), G. VAZQUEZ-GOMEZ, J. MATTHEWS, Jiří NEČA, Kateřina PĚNČÍKOVÁ (203 Česká republika), M. MACHALA a Jan VONDRÁČEK (203 Česká republika, garant)

Vydání

Toxicological sciences, OXFORD, OXFORD UNIV PRESS, 2018, 1096-6080

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10601 Cell biology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.564

Kód RIV

RIV/00216224:14310/18:00106522

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1093/toxsci/kfy153

UT WoS

000446112900020

Klíčová slova anglicky

aryl hydrocarbon receptor; polycyclic aromatic hydrocarbons; cytochrome P450 family 1; hydroxylated metabolites; estrogen receptor; cell cycle

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 23. 4. 2024 14:24, Mgr. Michal Petr

Anotace

V originále

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants that interact in a complex manner with both the aryl hydrocarbon receptor (AhR) and estrogen receptors (ER). Their potential endocrine-disrupting activities may depend on both inhibitory AhR-ER cross-talk and on AhR-dependent metabolic production of estrogenic PAH metabolites. Here, we analyzed the impact of AhR on estrogen-like effects of PAHs, such as benzotalpyrene (BaP), in particular, on control of cell cycle progression/cell proliferation. Using AhR knockout variant of estrogen-sensitive human breast cancer MCF-7 cells (MCF-7 AhR(KO) cells), we observed that the AhR-dependent control of cytochrome P450 family 1 (CYP1) expression played a major role in formation of estrogenic BaP metabolites, most notably 3-OH-BaP, which contributed to the ER-dependent induction of cell cycle progression/cell proliferation. Both BaP metabolism and the BaP-induced S-phase transition/cell proliferation were inhibited in MCF-7 AhR(KO) cells, whereas these cells remained sensitive towards both endogenous estrogen 17 beta-estradiol or hydroxylated BaP metabolites. BaP was found to increase the activity of ER-dependent luciferase reporter gene in wild-type MCF-7 cells; however, unlike its hydroxylated metabolite, BaP failed to stimulate luciferase activity in MCF-7 AhR(KO) cells. Similarly, estrogen-like effects of other known estrogenic PAHs, such as benzfajanthracene or 3-methylcholanthrene, were diminished in MCF-7 AhR(KO) cells. Ectopic expression of human CYP1A1 and CYP1B1 enzymes partly restored both BaP metabolism and its effects on cell proliferation. Taken together, our data suggest that the AhR-dependent metabolism of PAHs contributes significantly to the impact of PAHs on cell proliferation in estrogen-sensitive cells.

Citovat

HYZDALOVA, M., Jakub PIVNIČKA, Ondřej ZAPLETAL, G. VAZQUEZ-GOMEZ, J. MATTHEWS, Jiří NEČA, Kateřina PĚNČÍKOVÁ, M. MACHALA a Jan VONDRÁČEK. Aryl Hydrocarbon Receptor-Dependent Metabolism Plays a Significant Role in Estrogen-Like Effects of Polycyclic Aromatic Hydrocarbons on Cell Proliferation. Toxicological sciences. OXFORD: OXFORD UNIV PRESS, 2018, roč. 165, č. 2, s. 447-461. ISSN 1096-6080. Dostupné z: https://dx.doi.org/10.1093/toxsci/kfy153.

@article{1504024,
   author = {Hyzdalova, M. and Pivnička, Jakub and Zapletal, Ondřej and VazquezandGomez, G. and Matthews, J. and Neča, Jiří and Pěnčíková, Kateřina and Machala, M. and Vondráček, Jan},
   article_location = {OXFORD},
   article_number = {2},
   doi = {http://dx.doi.org/10.1093/toxsci/kfy153},
   keywords = {aryl hydrocarbon receptor; polycyclic aromatic hydrocarbons; cytochrome P450 family 1; hydroxylated metabolites; estrogen receptor; cell cycle},
   language = {eng},
   issn = {1096-6080},
   journal = {Toxicological sciences},
   title = {Aryl Hydrocarbon Receptor-Dependent Metabolism Plays a Significant Role in Estrogen-Like Effects of Polycyclic Aromatic Hydrocarbons on Cell Proliferation},
   url = {http://dx.doi.org/10.1093/toxsci/kfy153},
   volume = {165},
   year = {2018}
}

TY  - JOUR
ID  - 1504024
AU  - Hyzdalova, M. - Pivnička, Jakub - Zapletal, Ondřej - Vazquez-Gomez, G. - Matthews, J. - Neča, Jiří - Pěnčíková, Kateřina - Machala, M. - Vondráček, Jan
PY  - 2018
TI  - Aryl Hydrocarbon Receptor-Dependent Metabolism Plays a Significant Role in Estrogen-Like Effects of Polycyclic Aromatic Hydrocarbons on Cell Proliferation
JF  - Toxicological sciences
VL  - 165
IS  - 2
SP  - 447-461
EP  - 447-461
PB  - OXFORD UNIV PRESS
SN  - 10966080
KW  - aryl hydrocarbon receptor
KW  - polycyclic aromatic hydrocarbons
KW  - cytochrome P450 family 1
KW  - hydroxylated metabolites
KW  - estrogen receptor
KW  - cell cycle
UR  - http://dx.doi.org/10.1093/toxsci/kfy153
N2  - Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants that interact in a complex manner with both the aryl hydrocarbon receptor (AhR) and estrogen receptors (ER). Their potential endocrine-disrupting activities may depend on both inhibitory AhR-ER cross-talk and on AhR-dependent metabolic production of estrogenic PAH metabolites. Here, we analyzed the impact of AhR on estrogen-like effects of PAHs, such as benzotalpyrene (BaP), in particular, on control of cell cycle progression/cell proliferation. Using AhR knockout variant of estrogen-sensitive human breast cancer MCF-7 cells (MCF-7 AhR(KO) cells), we observed that the AhR-dependent control of cytochrome P450 family 1 (CYP1) expression played a major role in formation of estrogenic BaP metabolites, most notably 3-OH-BaP, which contributed to the ER-dependent induction of cell cycle progression/cell proliferation. Both BaP metabolism and the BaP-induced S-phase transition/cell proliferation were inhibited in MCF-7 AhR(KO) cells, whereas these cells remained sensitive towards both endogenous estrogen 17 beta-estradiol or hydroxylated BaP metabolites. BaP was found to increase the activity of ER-dependent luciferase reporter gene in wild-type MCF-7 cells; however, unlike its hydroxylated metabolite, BaP failed to stimulate luciferase activity in MCF-7 AhR(KO) cells. Similarly, estrogen-like effects of other known estrogenic PAHs, such as benzfajanthracene or 3-methylcholanthrene, were diminished in MCF-7 AhR(KO) cells. Ectopic expression of human CYP1A1 and CYP1B1 enzymes partly restored both BaP metabolism and its effects on cell proliferation. Taken together, our data suggest that the AhR-dependent metabolism of PAHs contributes significantly to the impact of PAHs on cell proliferation in estrogen-sensitive cells.
ER  -

HYZDALOVA, M., Jakub PIVNIČKA, Ondřej ZAPLETAL, G. VAZQUEZ-GOMEZ, J. MATTHEWS, Jiří NEČA, Kateřina PĚNČÍKOVÁ, M. MACHALA a Jan VONDRÁČEK. Aryl Hydrocarbon Receptor-Dependent Metabolism Plays a Significant Role in Estrogen-Like Effects of Polycyclic Aromatic Hydrocarbons on Cell Proliferation. \textit{Toxicological sciences}. OXFORD: OXFORD UNIV PRESS, 2018, roč.~165, č.~2, s.~447-461. ISSN~1096-6080. Dostupné z: https://dx.doi.org/10.1093/toxsci/kfy153.

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