Inhibition of citrus flavonoids on 12-O-tetradecanoylphorbol 13-acetate-induced skin inflammation and tumorigenesis in mice

The inhibitory effects of a formulated product from citrus peel extract, Gold Lotion (GL), on 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in mouse skin was reported in this study. It is found that in the TPA-induced skin inflammation model, the topical application of GL effectively inhibited the transcriptional activation of iNOS and its mRNA and protein in mouse skin. It is also discovered that GL significantly inhibited TPA-induced mouse skin inflammation by decreasing inflammatory gene parameters. Furthermore, GL dramatically inhibited 7,12-dimethylbenez[a]anthracene (DMBA)/TPA-induced skin tumor formation and reduced tumor incidence, tumor weight and tumor multiplicity of papillomas at 20 weeks. In essence, these in vivo data have revealed that GL is an effective anti-tumor agent that functions by down-regulating the protein levels of COX-2, ornithine decarboxylase (ODC), and vascular endothelial growth factor (VEGF) in mouse skin, suggesting that GL is a novel functional natural product capable of preventing inflammation-associated tumorigenesis.