All-trans retinoic acid modulates AHR signaling and its downstream target gene, CYP۱A 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, CYP۱A۱ by All-trans retinoic acid (ATRA) in human hepatoma cells (HepG۲ and Huh۷). The human hepatoma cell line (HepG۲-XRE-Luc) carrying cytochrome P۴۵۰۱A۱ (CYP۱A۱) response elements, HepG۲ and Huh۷ cells were exposed to different doses of ATRA (۱-۵۰ µM) and CYP۱A۱ transcription and enzymatic activities, as well as gene expression were measured. Our results showed that ATRA is able to induce CYP۱A۱ in an AHR-dependent manner using CH۲۲۳۱۹۱ as an AHR antagonist. The result showed that different doses of ATRA have no significant effects on cell viability.CYP۱A۱ enzyme and transcription activities as well as CYP۱A۱ 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.  Please cite this article as: Fereshteh Asadi Dolatabad, Sepideh Maghami, Najmeh Ekhtiyardar, Shadi Maghsodlo, Afshin Mohammadi-Bardbori. All-trans retinoic acid  modulates AHR signaling and its downstream target gene, CYP۱A in human hepatoma cells. Trends in Pharmaceutical Sciences. ۲۰۲۲;۸(۳):۱۲۷-۱۳۴. doi: ۱۱۰.۳۰۴۷۶/TIPS.۲۰۲۲.۹۴۱۶۶.۱۱۳۵.

Keywords:

All-trans Retinoic Acid , AHR signaling , CYP۱A , human hepatoma cells