Caffeic Acid Phenethyl Ester from the Twigs of Cinnamomum cassia Inhibits Malignant Cell Transformation by Inducing c-Fos Degradation

The twigs of Cinnamomum cassia, commonly referred to as Cinnamomi Ramulus, are widely used as one of the primary ingredients in Chinese/Korean traditional 9 medicines that have anticancer effects. However, the active constituents responsible for its anticancer effects and their molecular mechanisms still remain to be elucidated. Caffeic acid phenethyl ester (CAPE) and caffeic acid (CA) were isolated for the first time from C. cassia using LC-MS-guided phytochemical isolation methods. CAPE significantly suppressed EGF- and TPA-induced cell transformation of JB6 P+ cells at sub-micromolar concentrations, whereas CA, a structurally similar compound to CAPE, had no such effect. The antiproliferative and chemopreventive activity of CAPE was found to arise through the inhibition of AP-1 transcriptional activity via the promotion of c-Fos degradation. These findings demonstrate that CAPE may contribute to the chemopreventive/chemotherapeutic effects of C. cassia through downregulating c-Fos.