The purpose of the current study was to determine whether a tropical ginger derived compound1'-acetoxychavicol acetate (ACA), suppresses skin tumor promotion in K5.Stat3C mice. In a two-week study in which wild-type (WT) and K5.Stat3C mice were co-treated with either vehicle, ACA, galanga extract, or fluocinolone acetonide (FA) and tetradecanoyl phorbol acetate (TPA), only the galanga extract and FA suppressed TPA-induced skin hyperproliferation and wet weight. None of these agents were effective at suppressing p-Tyr705 Stat3 expression. However, ACA and FA showed promising inhibitory effects against skin tumorigenesis in K5.Stat3C mice. ACA also suppressed phospho-p65 NF-κB activation, suggesting a potential mechanism for its action. [ABSTRACT FROM AUTHOR]