Involvement of the antioxidative property of morusin in blocking phorbol ester-induced malignant transformation of JB6 P+ mouse epidermal cells

Chemoprevention has been acknowledged as an important and practical strategy for managing cancer. We have previously synthesized morusin, a prenylated flavonoid that exhibits anti cancer progression activity. In the present study, we evaluated the anti cancer promotion potential of morusin by using the mouse epidermal JB6 P+ cell model. Extensive evidence shows that tumor promotion by phorbol esters is due to the stimulation of reactive oxygen species (ROS). Therefore, the effect of morusin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ROS production was assessed. Noncytotoxic concentrations of morusin were found to dose-dependently reduce TPA -induced ROS production. Moreover, morusin inhibited TPA -induced activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappa B) activation, which can mediate cell proliferation and malignant transformation. Furthermore, morusin inhibited the TPA upregulation of cyclooxygenase 2 (COX-2), which may be regulated by AP-1 and NF-kappa B. In addition, noncytotoxic concentrations of morusin reduced the TPA-promoted cell growth of JB6 P+ cells and inhibited TPA -induced malignant properties, such as cytoskeletal rearrangement and cell migration of JB6 P+ cells. Similar to the effects of glutathione (GSH) pretreatment, morusin inhibited TPA -induced expression of N-cadeherin and vimentin, which are malignant cell surface proteins. Finally, morusin treatment dose-dependently suppressed the TPA -induced anchorage-independent cell transformation of JB6 P+ cells. In conclusion, our results evidence that morusin possesses anti cancer promotion potential because of its antioxidant property, which mediates multiple transformation associated gene expression. (C) 2017 Elsevier B.V. All rights reserved.