Cytotoxicity of hexahelicene and its effect on the aryl hydrocarbon receptor pathway

Abstract

Carbohelicenes are a group of helical-shaped polycyclic aromatic hydrocarbons. This study examined the effect of hexahelicene (or [6]helicene) and of its imidazolium derivative, 1-butyl-3-(2-methyl[6]helicenyl)-imidazolium bromide (I[6]H), on the activity of the aryl hydrocarbon receptor (AhR) and expression of cytochrome P450 1A1 (CYP1A1) in human hepatoma HepG2 cells. An MTT viability assay showed that both [6]helicene and I[6]H were cytotoxic to HepG2 cells after 24 h of exposure, with IC₅₀ values of 0.9 and 8.4 μM, respectively. Using a gene reporter assay performed in transiently transfected HepG2 cells, we found that 1 μM [6]helicene, unlike I[6]H, significantly increased the activity of AhR to 2.1-fold compared to the control after 24 h of exposure. Moreover, [6]helicene induced a small but significant increase in the level of CYP1A1 mRNA. On the other hand, neither the protein level nor activity of CYP1A1 were affected by [6]helicene in HepG2 cells. The effect of [6]helicene on the AhR pathway was thus much lower than that of 2,3,7,8-tetrachlorodibenzo-p-dioxin, a potent AhR activator. We conclude that [6]helicene is a poor activator of the AhR pathway in HepG2 cells, and that the possible activation of the AhR pathway in vivo remains to be investigated.

Keywords: Aryl hydrocarbon receptor; Biological activity; Cytochrome P450; Cytotoxicity; Helicene; PAH.