Effect of caffeic acid esters on carcinogen-induced mutagenicity and human colon adenocarcinoma cell growth

Propolis, a honey bee hive product, is thought to exhibit a broad spectrum of activities including antibiotic, antiviral, anti-inflammatory and tumor growth inhibition; some of the observed biological activities may be due to caffeic acid (cinnamic acid) esters that are present in propolis. In the present study we synthesized three caffeic acid esters, namely methyl caffeate (MC), phenylethyl caffeate (PEC) and phenylethyl dimethylcaffeate (PEDMC) and tested them against the 3,2′-dimethyl-4-aminobiphenyl, (DMAB, a colon and mammary carcinogen)-induced mutagenecity in Salmonella typhimurium strains TA 98 and TA 100. Also, the effect of these agents on the growth of human colon adenocarcinoma, HT-29 cells and activities of ornithine decarboxylase (ODC) and protein tyrosine kinase (PTK) was studied. Mutagenicity was induced in Salmonella typhimurium strains TA 98 and TA 100 plus S₉ activation using 5 and 10 μg DMAB and antimutagenic activities of 0-150 μM MC, 0-60 μM PEC and 0-80 μM PEDMC were determined. The results indicate that MC, PEC and PEDMC were not mutagenic in the Salmonella tester system. DMAB-induced mutagenicity was significantly inhibited with 150 μM MC, 40-60 μM PEC and 40-80 μM PEDMC in both tester systems. Treatment of HT-29 colon adenocarcinoma cells with > 150 μM MC, 30 μM PEC and 20 μM PEDMC significantly inhibited the cell growth and syntheses of RNA, DNA and protein. ODC and PTK activities were also inhibited in HT-29 cells treated with different concentrations of MC, PEC and PEDMC. These results demonstrate that caffeic acid esters which are present in Propolis possess chemopreventive properties when tested in shortterm assay systems.