The effects of lingonberry (Vaccinium vitis-idaea L.) extracts on activator protein-1 (AP-1), nuclear factor-kappaB (NF-κB), and mitogen-activated protein kinases (MAPKs) were evaluated. Pretreatment of JB6 P+ mouse epidermal cells with lingonberry extracts produced a dose-dependent inhibition of AP-1 and NF-κB induced by either 12-O-tetradecanoylphorbol-13-acetate (TPA) or ultraviolet-B (UVB) light. Lingonberry extracts blocked UVB-induced phosphorylation of MAPK family members ERK1, ERK2, and p38, but not JNK. Lingonberry extracts also prevented TPA-induced phosphorylation of ERK1 and ERK2. Results of soft agar assays indicated that lingonberry extracts suppressed TPA-induced neoplastic transformation of JB6 P+
cells in a dose-dependent manner. Lingonberry extracts also induced the apoptosis of human leukemia HL-60 cells in a dose-independent manner. These results suggest that ERK1 and ERK2 may be inhibited by lingonberries, which results in suppression of AP-1 and neoplastic transformation in JB6 P+ cells and causes cancer cell death by an apoptotic mechanism in human leukemia HL-60 cells.