Inhibitory Effect on Activator Protein-1, Nuclear Factor-KappaB, and Cell Transformation by Extracts of Strawberries (Fragaria × ananassa Duch.)

Abstract

The inhibitory effects of strawberry (Fragaria × ananassa Duch.) antioxidant enzymes on tetradecanoylphorbol-13-acetate (TPA) or ultraviolet-B (UVB) induced activator protein-1 (AP-1) and nuclear factor-kappaB (NF-κB) were studied. The inhibitory effects of strawberry extracts on the proliferation and transformation of human and mouse cancer cells were also evaluated. Strawberries had high activities of glutathione peroxidase, superoxide dismutase, guaiacol peroxidase, ascorbate peroxidase, and glutathione reductase. Strawberry extracts inhibited the proliferation of human lung epithelial cancer cell line A549 and decreased TPA-induced neoplastic transformation of JB6 P⁺ mouse epidermal cells. Pretreatment of JB6 P⁺ mouse epidermal cells with strawberry extract resulted in the inhibition of both UVB- and TPA-induced AP-1 and NF-κB transactivation. Furthermore, strawberry extract also blocked TPA-induced phosphorylation of extracellular signal-regulated kinases (ERKs) and UVB-induced phosphorylation of ERKs and JNK kinase in JB6 P⁺ mouse epidermal cell culture. These results suggest that the ability of strawberries to block UVB- and TPA-induced AP-1 and NF-κB activation may be due to their antioxidant properties and their ability to reduce oxidative stress. The oxidative events that regulate AP-1 and NF-κB transactivation can be important molecular targets for cancer prevention. The strawberries may be highly effective as a chemopreventive agent that acts by targeting the down-regulation of AP-1 and NF-κB activities, blocking MAPK signaling, and suppressing cancer cell proliferation and transformation. Keywords: Antioxidant enzymes; activator protein-1; nuclear factor-kappaB; mitogen-activated protein kinase; neoplastic transformation; Fragaria × ananassa Duch.