Hexachlorobenzene pesticide exposure upregulates the expression of kynurenine pathway enzymes in vitro, and promotes immunosuppression in the experimental HER2-positive breast cancer model

ZÁRATE LV; PEÑA AGUDELO JA; MIRET NV; NICOLA CANDIA AJ; ZAPPIA CD; CHIAPPINI FA; PONTILLO CA; MONCZOR F; CANDOLFI M; RANDI A

Congreso; Reunión Anual de Sociedades de Biociencias 2022; 2022

SAIC

Breast cancer is the most common cancer in women worldwide. Among the proposed risk factors, environmental pollutants are increasingly involved in metastatic tumor cells emergence and progression. Hexachlorobenzene (HCB) pesticide is a weak ligand of the Aryl Hydrocarbon Receptor (AhR), a transcription factor related to tumor development. Previously, we have reported that HCB promotes cell proliferation, migration and invasion in breast cancer cells. Accumulating evidence confirms that IDO1/TDO2 overexpression in tumor leads to tryptophan depletion in the microenvironment, activating Kynurenine pathway, and suppressing the T-cell mediated immune response. In this study, we have examined the action of HCB exposure (0.03, 0.3 and 3 mg/kg body weight, bw) in a syngeneic mouse model of HER2+ breast cancer (ER-/PR-/HER2+) for 15 and 30 days. In addition, we have evaluated the effect of HCB (0.005; 0.05; 0.5 and 5 μM) on LM3 cells for 24 h. Results show that HCB exposure in LM3 enhanced AhR protein levels at all doses (p