Antioxidative and antitumor promoting effects of [6]-paradol and its homologs

Recently, considerable attention is focused on anti-carcinogenic phytochemicals, particularly those derived from medicinal or edible plants. [6]-Paradol, a pungent phenolic compound present in certain Zingiberaceae plants, is known to have antimicrobial and analgesic activities. The compound has been reported to attenuate promotion of skin carcinogenesis and TPA-induced ear edema in female ICR mice, and to induce apoptosis in cultured human promyelocytic leukemia (HL-60) cells. In this study, we performed several biochemical studies to evaluate and compare the cancer chemopreventive potential of [6]-paradol and its synthetic derivatives. [6]-Paradol and its synthetic nonpungent analog, [6]-dehydroparadol significantly decreased the incidence and the multiplicity of skin tumors initiated by 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by 12-0-tetradecanoylphorbol-13-acetate (TPA). Topical application of [6]-paradol and its derivatives inhibited TPA-induced ear edema and H2O2 production and myeloperoxidase activity in the dorsal skin of mice. Induction of TPA-induced mouse epidermal ornithine decarboxylase (ODC) activity and H2O2- and UV-induced formation of oxidized DNA bases in vitro were also attenuated by the above compounds. These results indicate that [6]-paradol and its derivatives possess the cancer chemopreventive potential. (C) 2001 Elsevier Science B.V. All rights reserved.