In this study, we investigated the antiproliferative activity and the stability and metabolic fate of the main dietary hydroxycinnamates, using two colonic adenocarcinoma cell models (Caco-2 and SW480). Dihydrocaffeic and dihydroferulic acids were the most effective against cell proliferation in both cell lines with IC50 values of 71.7 ± 1.1 and 83.1 ± 1.1 μmol/L, respectively ( P < 0.05) in Caco-2. At 200 μmol/L, caffeic and ferulic acids inhibited SW480 proliferation by 40.8 ± 1.6 and 59.9 ± 1.3%, respectively. Hydroxycinnamic acids with a catechol-type structure were degraded in Caco-2 cell medium, resulting in the production of H2O2. Intracellular Caco-2 UDP-glucuronosyltransferases and catechol- O-methyltransferases were able to form glucuronide and methyl conjugates. However, only the sulfate conjugates were detected after incubation with SW480. In addition, simple hydroxycinnamates were released from quinic and aspartic conjugates. The remarkable effect of dihydrocaffeic and dihydroferulic acids against cell proliferation is of paramount importance, since these compounds are the main metabolites detectable at the colonic level.
Keywords: antiproliferative activity; colon cancer; mass spectrometry; metabolism; phenolic compounds.