INHIBITORY EFFECTS OF CAFFEIC ACID PHENETHYL ESTER (CAPE) ON 12-O-TETRADECANOYLPHORBOL-13-ACETATE-INDUCED TUMOR PROMOTION IN MOUSE SKIN ANDTHE SYNTHESIS OF DNA, RNA AND PROTEIN IN HELA-CELLS

Topical application of caffeic acid phenethyl ester (CAFE), a constitu ent of the propolis of honeybee hives, to the backs of CD-1 mice previ ously initiated with 7,12-dimethylbenz[a]anthracene (DMBA) inhibited 1 2-O-tetradecanoylphorbol-13-acetate (TPA)-induced tumor promotion and the formation of 5-hydroxymethyl-2'-deoxyuridine (HMdU) in epidermal D NA. Topical application of 5 nmol TPA twice weekly for 20 weeks to mic e previously initiated with 200 nmol of DMBA resulted in 18.8 skin pap illomas per mouse. Topical application of 1, 10, 100 or 3000 nmol of C AFE together with 5 nmol of TPA twice a week for 20 weeks inhibited th e number of skin papillomas per mouse by 24, 30, 45 or 70%, respective ly, and tumor size per mouse was decreased by 42, 66, 53 or 74%, respe ctively. Topical application of 5 nmol of TPA twice weekly for 20 week s to mice previously initiated with DMBA produced an average of 12.6 H MdU residues per 10(4) normal bases in epidermal DNA. Topical applicat ion of 1, 10, 100 or 3000 mmol of CAFE with 5 nmol of TPA twice weekly for 20 weeks to DMBA-initiated mice decreased the level of HMdU in ep idermal DNA by 40-93%. The in vitro addition of 1.25, 2.5, 5, 10 or 20 mu M CAPE to cultured HeLa cells inhibited the synthesis of DNA by 32 , 44, 66, 79 or 95%, respectively, the synthesis of RNA was inhibited by 39, 43, 58, 64 or 75%, respectively, and the synthesis of protein w as inhibited by 29, 30, 37, 32 or 47%, respectively. The results indic ate a potent inhibitory effect of CARE on TPA-induced tumor promotion and TPA-induced formation of HMdU in DNA of mouse skin as well as an i nhibitory effect of CAFE on the synthesis of DNA, RNA and protein in c ultured HeLa cells.