CAFFEIC ACID PHENETHYL ESTER INHIBITS PROLIFERATION OF HUMAN KERATINOCYTES AND INTERFERES WITH THE EGF REGULATION OF ORNITHINE DECARBOXYLASE

Caffeic acid phenethyl ester (CAFE) was evaluated for its potential in regulating keratinocyte proliferation. CAFE inhibited the proliferati on of SV40 transformed keratinocytes (Z114) in a concentration- and ti me-dependent manner. Inhibition by CAFE was seen with 0.5 to 5.0 mu g/ ml at 48 h. Cell toxicity was observed at 10 mu g/ml by changes in mor phology and decreased viability. Pretreatment of 2114 cells with CAFE significantly prevented the full induction of ornithine decarboxylase (ODC) by epidermal growth factor (EGF) in a concentration-and time-dep endent manner. Inhibition was observed with a concentration of CAFE as low as 1 mu g/ml, and complete inhibition of ODC induction by EGF occ urred at 5 mu g/ml. Northern analysis showed that treatment of cells w ith CAFE for 24 h suppressed EGF induction of ODC gene expression. Inc ubation of 2114 cells with CAFE for 24 h resulted in a concentration-d ependent decrease in EGF binding and a 30% reduction in the EGF induce d autophosphorylation of the EGF receptor. CAFE decreased both membran ous and cytosolic PKC activity in a concentration- and time-dependent manner. Because significant inhibition of keratinocyte proliferation o ccurred at concentrations of CAFE that interfered with PKC activity an d EGF signal transduction but did not cause overt toxicity, CAFE may p rove useful for the treatment of hyperproliferative skin diseases.