Breast cancer progression and kynurenine pathway enzymes are induced by hexachlorobenzene exposure in a Her2-positive model.
Lorena V ZárateNoelia V MiretAlejandro J Nicola CandiaC Daniel ZappiaCarolina A PontilloFlorencia A ChiappiniFederico MonczorMarianela CandolfiAndrea S RandiPublished in: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (2023)
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.
Keyphrases
- estrogen receptor
- positive breast cancer
- epidermal growth factor receptor
- vascular endothelial growth factor
- endothelial cells
- papillary thyroid
- squamous cell
- childhood cancer
- poor prognosis
- advanced non small cell lung cancer
- breast cancer risk
- tyrosine kinase
- endoplasmic reticulum
- binding protein
- cell cycle arrest
- signaling pathway
- long non coding rna
- oxidative stress
- pregnant women
- young adults
- biofilm formation
- nitric oxide
- pseudomonas aeruginosa
- endoplasmic reticulum stress
- simultaneous determination
- candida albicans