Figure 7, top panel, shows a representative Western blot JPH203 for the active form of Stat3 expression,

i.e. phosphorylated Stat3 at tyrosine residue 705. In Figure 7, middle panel, the experimental data for the phosphorylated Stat3 expression in WT mice are shown. As evident from the data presented, TPA treatment did not significantly increase the expression of phosphorylated Stat3 in comparison to the vehicle control. It could be that activation of Stat3 occurred earlier than 48 h. Moreover, neither the synthetic ACA nor the galanga extract was effective in modulating the expression of phosphorylated Stat3. The effect of FA was not significantly different from the TPA treated group. In Figure 7, lower panel, data for the K5.Stat3C 17DMAG datasheet transgenic mice only are shown. An important point to be considered is that these mice have constitutive expression of Stat3 in the epidermal keratinocytes which also means these mice have the active Stat3 or phosphorylated Stat3 signal already turned on. Therefore, these mice have higher basal levels of the phosphorylated Stat3 protein as compared to the basal levels of this protein in the wild type mice. Once again, TPA did

not increase the expression of phosphorylated Stat3 in the transgenic mice. Furthermore, neither synthetic Selumetinib cost ACA nor the galanga extract was able to modulate the expression of the phosphorylated Stat3 protein in the transgenic mice. Even FA was not able to shut off the activated Stat3 signal in the transgenic mice and thus did not modulate the expression of phosphorylated Stat3 as it did in the wild type mice previously. Effects of ACA and FA on skin carcinogenesis in WT vs. K5.Stat3C mice Finally, the effects of ACA on DMBA/TPA-induced tumorigenesis were examined in K5.Stat3C transgenic mice (Tables 1–2, Figure 8). In the K5.Stat3C mice treated with TPA only, lesions began to appear between 5–16 weeks of promotion and reached a maximum at 21 weeks. This experiment was terminated

at 21 weeks due to morbidity in the TPA only mice. Statistical analyses of the histopathology are summarized in Tables 1–2. Overall, there were fewer carcinomas in-situ than invasive SCCs (Table 2). The percentages IMP dehydrogenase of mice with carcinomas in-situ were not statistically significant (Table 1). However, the percentages of mice with invasive SCC’s were significantly different, with the FA/TPA group being significant and the ACA/TPA group being marginal, suggesting that more subjects in the ACA/TPA group might have revealed a difference. Histopathological analyses revealed an average of 1.21 ± 0.38 carcinomas in-situ and 3.07 ± 0.61 invasive SCC’s per mouse in the TPA only group (Table 2). There was no significant difference in the average numbers of carcinomas in-situ.