Effects of polyphenols derived from fruit of Crataegus pinnatifida on cell transformation, dermal edema and skin tumor formation by phorbol ester application

Abstract

The dried fruits of Crataegus pinnatifida have been used traditionally as oriental medicine and local soft drink material recently. Previously, we demonstrated that C. pinnatifida exhibited anti-oxidation and anti-inflammatory potential. To clarify the active components in anti-transformation and anti-tumor promotion, we collected the polyphenol fraction (CF-TP) of hot-water extracts from dried fruits of C. pinnatifida for the following study. By anchorage-independent transformation assay, CF-TP significantly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell transformation in JB6 P(+) cells. Moreover, we found that CF-TP inhibited the expression of osteopontin (OPN), a transformational marker, and the activation of NF-kappaB and AP-1 induced by TPA in JB6 P(+) cells. In addition, we evaluated the effect of CF-TP on TPA application to ICR mouse skin with measurement of H(2)O(2) production, myeloperoxidase (MPO) activity, edema formation, epidermal thickness and leukocyte infiltration. As a result, CF-TP significantly inhibited the generation of reactive oxygen species (ROS) and the phenomena of inflammation induced by TPA. It also suppressed the expression of COX-2 and iNOS, and the activation of ornithine decarboxylase (ODC). Furthermore, CF-TP inhibited benzo[a]pyrene (B[a]P)/TPA-induced skin tumor formation and decreased the incidence of tumor. These results indicate that CF-TP possesses potential as a cancer chemopreventive agent against tumor promotion.