Benzopyrene Inhibits Differentiation of Human SH-SY5Y Neuroblastomain Culture in Cells

Abstract

Benzopyrene (BaP) is polycyclic aromatic hydrocarbon (PAH), and is chemically modified in the animal body to form a number of metabolites that may elicit a various toxicity. However, the effect of BaP on neuroblastoma differentiation has remained unclear. We have studied the effect of BaP on neurite outgrowth using human SH-SY5Y neuroblastoma cells induced to differentiate by all-trans-retinoic acid (RA). Whereas BaP, at a concentration of 1 μM, had no significant effect on the viability of differentiating SH-SY5Y cells, the neurite outgrowth of differentiating SH-SY5Y cells 48 h after BaP treatment was significantly inhibited. Treatment of RA-stimulated differentiating SH-SY5Y cells with 0.1-3 μM BaP resulted in decreased level of cross-reactivities with tissue glutaminase (TGase) antibody in a dose-dependent manner. To investigate the involvement of AhR signaling in the inhibition of neurite outgrowth of differentiating neuroblastoma cells by BaP, we used AhR antagonists, α-Naphthoflavone and CH223191. Cotreatment of α-Naphthoflavone (1 μM) to BaP-treated SH-SY5Y cells recovered the expression level of TGase protein up to 200% of control. Like α-Naphthoflavone, another potent AhR antagonist, CH223191 (0.1 to 1 μM) also recovered the inhibition effects of BaP on neurite outgrowth and TGase expression level of neuroblastoma cells. These results suggested that AhR signaling should be involved in the inhibition process of BaP on RA-induced differentiation of SH-SY5Y neuroblastoma cells.