Protective Effect of Mulberry (Morus alba L.) Extract against Benzo[a]pyrene Induced Skin Damage through Inhibition of Aryl Hydrocarbon Receptor Signaling

Benzo­[a]­pyrene (B­[a]­P), a type of polycyclic aromatic hydrocarbon, is present in the atmosphere surrounding our environment. Although B­[a]P is a procarcinogen, enzymatically metabolized benzo­[a]­pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) could intercalate into DNA to form bulky BPDE-DNA adducts as an ultimate carcinogenic product in human keratinocytes. The aim of this study was to evaluate the protective effect of mulberry extract, purified from the fruit of Morus Alba L., on B­[a]­P-induced cytotoxicity in human keratinocytes and its mechanisms of action. In this study, we confirmed that B­[a]P induced nuclear translocation and the activation of aryl hydrocarbon receptor (AhR) were decreased by pretreatment of mulberry extract. Mulberry extract could decrease DNA damage through the suppression of B­[a]P derived DNA adduct formation and restoration of cell cycle retardation at S phase in a dose-dependent manner. Additionally, cyanidin-3-glucoside (C3G), a major active compound of mulberry extract, showed biological activities to protect the cells from B­[a]P exposure, similar to the effectivity of the mulberry extract. These results indicated that the inhibitory effect of C3G against B­[a]P inducing skin cancer is attributable to repress the AhR signaling pathway.