All-trans retinoic acid modulates AHR signaling and its downstream target gene, CYP1A in human hepatoma cells

The aryl hydrocarbon receptor (AHR) was identified for its mediating toxicological role in response to variety of the polycyclic aromatic hydrocarbon family of environmental contaminants however, recent data indicate that the AHR can be activated with different types of endogenous and exogenous chemicals. The aim of this study was to gain more information about the mechanisms that regulate expression of the AHR target gene, CYP1A1 by All-trans retinoic acid (ATRA) in human hepatoma cells (HepG2 and Huh7). The human hepatoma cell line (HepG2-XRE-Luc) carrying cytochrome P4501A1 (CYP1A1) response elements, HepG2 and Huh7 cells were exposed to different doses of ATRA (1-50 μM) and CYP1A1 transcription and enzymatic activities, as well as gene expression were measured. Our results showed that ATRA is able to induce CYP1A1 in an AHR-dependent manner using CH223191 as an AHR antagonist. The result showed that different doses of ATRA have no significant effects on cell viability.CYP1A1 enzyme and transcription activities as well as CYP1A1 mRNA for all treated group showed a significant elevation by ATRA. To better understand the mechanism underlying AHR activation by ATRA more molecular studies are needed.