Cell transformation induced by
epidermal growth factor (
EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) is a critical event in
cancer initiation and progression, and understanding the underlying mechanisms is essential for the development of new therapeutic strategies. Licorice extract contains various bioactive compounds, which have been reported to have anticancer and anti-inflammatory effects. This study investigated the
cancer preventive efficacy of
licochalcone D (LicoD), a
chalcone derivative in licorice extract, in
EGF and TPA-induced transformed skin keratinocyte cells. LicoD effectively suppressed
EGF-induced cell proliferation and anchorage-independent colony growth.
EGF and TPA promoted the S phase of cell cycle, while LicoD treatment caused G1 phase arrest and down-regulated
cyclin D1 and up-regulated p21 expression associated with the G1 phase. LicoD also induced apoptosis and increased apoptosis-related
proteins such as cleaved-caspase-3, cleaved-caspase-7, and Bax (Bcl-2-associated X protein). We further investigated the effect of LicoD on the AKT signaling pathway involved in various cellular processes and found decreased p-AKT, p-GSK3β, and p-NFκB expression. Treatment with
MK-2206, an AKT pharmacological inhibitor, suppressed
EGF-induced cell proliferation and transformed colony growth. In conclusion, this study demonstrated the potential of LicoD as a preventive agent for skin
carcinogenesis.