Biomol Ther.  2021 Mar;29(2):227-233. 10.4062/biomolther.2020.083.

Mechanisms of Resorcinol Antagonism of Benzo[a]pyrene-Induced Damage to Human Keratinocytes

• Lee SE
• Kwon K
• Oh SW
• Park SJ
• Yu E
• Kim H
• Yang S
• Park JY
• Chung WJ
• Cho JY
• Lee J

• KMID: 2513491
• DOI: http://doi.org/10.4062/biomolther.2020.083

Abstract

Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon and ubiquitous environmental toxin with known harmful effects to human health. Abnormal phenotypes of keratinocytes are closely associated with their exposure to B[a]P. Resorcinol is a component of argan oil with reported anticancer activities, but its mechanism of action and potential effect on B[a]P damage to the skin is unknown. In this study, we investigated the effects of resorcinol on B[a]P-induced abnormal keratinocyte biology and its mechanisms of action in human epidermal keratinocyte cell line HaCaT. Resorcinol suppressed aryl hydrocarbon receptor (AhR) activity as evidenced by the inhibition of B[a]P-induced xenobiotic response element (XRE)-reporter activation and cytochrome P450 1A1 (CYP1A1) expression. In addition, resorcinol attenuated B[a]P-induced nuclear translocation of AhR, and production of ROS and pro-inflammatory cytokines. We also found that resorcinol increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activity. Antioxidant response element (ARE)-reporter activity and expression of ARE-dependent genes NAD(P)H dehydrogenase [quinone] 1 (NQO1), heme oxygenase-1 (HO-1) were increased by resorcinol. Consistently, resorcinol treatment induced nuclear localization of Nrf2 as seen by Western analysis. Knockdown of Nrf2 attenuated the resorcinol effects on ARE signaling, but knockdown of AhR did not affect resorcinol activation of Nrf2. This suggests that activation of antioxidant activity by resorcinol is not mediated by AhR. These results indicate that resorcinol is protective against effects of B[a]P exposure. The mechanism of action of resorcinol is inhibition of AhR and activation of Nrf2-mediated antioxidant signaling. Our findings suggest that resorcinol may have potential as a protective agent against B[a]P-containing pollutants.

Keyword

Resorcinol; AhR; ARE; HO-1; Nrf2; XRE