Involvement of peroxisome proliferator-activated receptor gamma (PPARγ) and autophagic pathways in the mechanism of action of the tris(2,3-dibromopropyl) isocyanurate (TDBP-TAZTO or TBC) flame retardant in the lung adenocarcinoma (A549) cells in vitro

Tris(2,3-dibromopropyl) isocyanurate (TDBP-TAZTO or TBC) belongs to the class of novel brominated flame retardants. TBC is relatively easily released from products both during production and use; hence, it has been detected in various environmental samples. It has also been reported that TBC causes toxic effects in different cell types and now its mechanism of action is connected with oxidative stress. However, the molecular mechanism of the TBC action is mostly unknown. The aim of this study was to determine the involvement of the PPAR gamma receptor and certain autophagic proteins (mTOR and p62) in the mechanism of the TBC action in adenocarcinomic human alveolar basal epithelial cells (A549) in vitro. Our study showed that TBC induced toxicity only at the highest micromolar concentrations (10, 50, and 100 mu M) in human A549 cells, which are a well-established model of the alveolar type II pulmonary epithelium. TBC probably induced apoptosis only at the 50- and 100-mu M concentrations. However, in our experimental model, TBC showed the ability to trigger oxidative stress and affected the mRNA expression of antioxidant enzymes (SOD1 and CAT) at the lower concentrations (1 and 10 mu M) than in the case of apoptosis, suggesting that the apoptosis was ROS independent. Our experiments with the PPAR gamma agonist (rosiglitazone) and antagonist (GW9662) suggests that TBC acted in the A549 cell line probably through activation of the mTOR-PPAR gamma pathway and could interfere with the p62 autophagy pathway.

Automated summary

This study investigated the mechanism of action of TBC in adenocarcinomic human alveolar basal epithelial cells, suggesting that TBC induced cell toxicity and apoptosis at high concentrations, but triggered oxidative stress and affected antioxidant enzyme expression at lower concentrations. Additionally, TBC likely acted through activation of the mTOR-PPARγ pathway and may interfere with the p62 autophagy pathway.