Inhibition of mouse skin tumor promotion by anti-inflammatory diarylheptanoids derived from Alpinia oxyphylla Miquel (Zingiberaceae).

Alpinia oxphylla Miquel, which belongs to the ginger family (Zingiberaceae), has been used in Oriental herbal medicine. Our recent studies have revealed that the methanolic extract of A. oxyphylla suppresses mouse skin tumor promotion and induces apoptosis in cultured human promyelocytic leukemia cells. In the present work, we have assessed effects of yakuchinone A and yakuchinone B, phenolic diarylheptanoids derived from A. oxyphylla, on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation and epidermal ornithine decarboxylase (ODC) activity as well as on skin tumor promotion in female ICR mice. Thus, topical application of 2 or 6 micromol of the diarylheptanoids prior to each topical dose of TPA significantly ameliorated 7,12-dimethylbenz[a]anthracene-initiated mouse skin tumor formation. In parallel with suppression of tumor promotion, topically applied yakuchinone A and B markedly inhibited TPA-induced epidermal ODC activity and ODC mRNA expression. In another experiment, yakuchinone A and B reduced production of tumor necrosis factor-alpha in TPA-stimulated mouse skin. Furthermore, both compounds inhibited the TPA-induced expression of cyclooxygenase-2 at both transcriptional and translational levels. These findings indicate that pungent diarylheptanoids from A. oxyphylla Miquel have an antitumor promotional activity that might be related to their anti-inflammatory properties.