Ear edema induced by the topical application of TPA is suppressed by pre-treatment with Xanthorrhizol in a doserelated manner (P<0.005). Topical application of Xanthorrhizol alone does not induce ear edema in mice. All the mice treated with 7.5 nM TPA for 19 weeks after initiation by DMBA developed an average of 15.5±2.3 skin tumors per mouse (tumor multiplicity). Pre-treatment with 2 and 6 μM Xanthorrhizol reduces tumor multiplicity to 6.9±1.1 (P<0.005) and 4.0±1.1 (P<0.005), respectively, at 19 weeks. In addition, Xanthorrhizol at 2 and 6 μM dose dependently lowers the percentage of tumor-bearing mice (tumor incidence) to 80 and 57%, respectively, at the termination of the experiments. Furthermore, the tumor multiplicity (P<0.05) and incidence are reduced in the DMBA-initiated mice that are topically treated with Xanthorrhizol for 6 weeks after the induction of papillomas with hyperplasia, mild dysplasia and moderate dysplasia by topical TPA application for 6, 18 and 24 weeks, respectively. The increased ODC expression in mouse epidermis with acute inflammation and tumor promotion induced by TPA is inhibited by pre-treatment with Xanthorrhizol in a dose-dependent manner. The topical application of Xanthorrhizol after the induction of papillomas with hyperplasia and dysplasia also potently inhibited ODC expression.
