Novel Insights into the Biomolecular Mechanism of Action of 4-Geranyloxyferulic Acid, a Colon Cancer Chemopreventive Agent

In this manuscript the biomolecular mechanism of action of the natural colon cancer chemopreventive agent 4′-geranyloxyferulic acid in cultured Caco-2 cells has been investigated. It was first demonstrated how the application of this phytochemical led to a time- and dose-dependent decrease of cell viability and in parallel to a massive generation of reactive oxygen species and induction of caspases 3 and 9, finally providing apoptosis. This event is accompanied by deep modifications in key pro-apoptotic targets like CD95, DR4 and 5, cytochrome c, Apaf-1, Bcl-2, and Bax. Such effects can explain the large apoptosis recorded in Caco-2 cells treated with 4′-geranyloxyferulic acid.