Breast cancer progression and kynurenine pathway enzymes are induced by hexachlorobenzene exposure in a Her2-positive model.

Autor: Zárate LV; Universidad de Buenos Aires, Facultad de Medicina, Departamento de Bioquímica Humana, Laboratorio de Efectos Biológicos de Contaminants Ambientales, Paraguay 2155, Piso 5, (CP 1121), Buenos Aires, Argentina. Electronic address: zaratelorenav@gmail.com., Miret NV; Universidad de Buenos Aires, Facultad de Medicina, Departamento de Bioquímica Humana, Laboratorio de Efectos Biológicos de Contaminants Ambientales, Paraguay 2155, Piso 5, (CP 1121), Buenos Aires, Argentina; Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Físico-Matemática, Laboratorio de Radioisótopos, Junín 954, 1er Subsuelo, (CP 1121), Buenos Aires, Argentina. Electronic address: nmiret@fmed.uba.ar., Nicola Candia AJ; Universidad de Buenos Aires, Facultad de Medicina, Instituto de Investigaciones Biomédicas, Laboratorio de Inmunoterapia Antitumoral, Paraguay 2155, Piso 10, (CP 1121), Buenos Aires, Argentina. Electronic address: alenicola90@gmail.com., Zappia CD; Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Investigaciones Farmacológicas (UBA-CONICET), Laboratorio de Farmacología de Receptores, Junín 954, Planta Baja, (CP1113), Buenos Aires, Argentina. Electronic address: danielzappia@hotmail.com., Pontillo CA; Universidad de Buenos Aires, Facultad de Medicina, Departamento de Bioquímica Humana, Laboratorio de Efectos Biológicos de Contaminants Ambientales, Paraguay 2155, Piso 5, (CP 1121), Buenos Aires, Argentina. Electronic address: caropontillo@gmail.com., Chiappini FA; Universidad de Buenos Aires, Facultad de Medicina, Departamento de Bioquímica Humana, Laboratorio de Efectos Biológicos de Contaminants Ambientales, Paraguay 2155, Piso 5, (CP 1121), Buenos Aires, Argentina. Electronic address: florenciachiappini@hotmail.com., Monczor F; Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Investigaciones Farmacológicas (UBA-CONICET), Laboratorio de Farmacología de Receptores, Junín 954, Planta Baja, (CP1113), Buenos Aires, Argentina. Electronic address: monczorf@gmail.com., Candolfi M; Universidad de Buenos Aires, Facultad de Medicina, Instituto de Investigaciones Biomédicas, Laboratorio de Inmunoterapia Antitumoral, Paraguay 2155, Piso 10, (CP 1121), Buenos Aires, Argentina. Electronic address: maru.candolfi@gmail.com., Randi AS; Universidad de Buenos Aires, Facultad de Medicina, Departamento de Bioquímica Humana, Laboratorio de Efectos Biológicos de Contaminants Ambientales, Paraguay 2155, Piso 5, (CP 1121), Buenos Aires, Argentina. Electronic address: andybiol@yahoo.com.ar.
Jazyk: angličtina
Zdroj: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association [Food Chem Toxicol] 2023 Jul; Vol. 177, pp. 113822. Date of Electronic Publication: 2023 May 09.
DOI: 10.1016/j.fct.2023.113822
Abstrakt: Breast cancer is one of the leading cancers among women worldwide. Given the evidence that pesticides play an important role in breast cancer, interest has grown in pesticide impact on disease progression. Hexachlorobenzene (HCB), an aryl hydrocarbon receptor (AhR) ligand, promotes triple-negative breast cancer cell migration and invasion. Estrogen receptor β (ERβ) inhibits cancer motility, while G protein-coupled ER (GPER) modulates the neoplastic transformation. Tryptophan is metabolized through the kynurenine pathway by indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO), with kynurenine signaling activation often predicting worse prognosis in cancer. In this context, we examined the HCB (0.005; 0.05; 0.5 and 5 μM) effect on LM3 cells, a human epidermal growth factor receptor 2 (HER2)-positive breast cancer model. Results show that HCB increases IDO and TDO mRNA levels and promotes cell viability, proliferation and migration through the AhR pathway. Moreover, HCB boosts mammosphere formation, vascular endothelial growth factor and cyclooxygenase-2 expression and reduces IL-10 levels. For some parameters, U-shaped or inverted U-shaped dose-response curves are shown. HCB alters ER levels, reducing ERβ while increasing GPER. These results demonstrate that exposure to environmentally relevant concentrations of HCB up-regulates the kynurenine pathway and dysregulates ERβ and GPER levels, collaborating in HER2-positive breast cancer progression.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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