4--geranyloxyferulic-acid and Colonic-Neoplasms

3-(4'-Geranyloxy-3'-methoxyphenyl)-2-trans propenoic acid (4'-geranyloxyferulic acid, GOFA) is a secondary metabolite biosynthetically related to ferulic acid in which a geranyl chain is attached to the phenolic group, extracted in 1966 from Acronychia baueri Schott (Fam. Rutaceae). In the last decade the pharmacological properties of the title compound began to be characterized, revealing its good activity as anti-inflammatory and dietary feeding cancer chemopreventive agent. The aim of this review is to examine in detail the recently reported properties of 4'-geranyloxyferulic acid from a chemical and pharmacological point of view, including the recent acquisition about its mechanism of action.

Topics: Anti-Bacterial Agents; Anticarcinogenic Agents; Colonic Neoplasms; Coumaric Acids; Humans; Neuroprotective Agents; Rutaceae

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.

Topics: Apoptosis; Caco-2 Cells; Caspases; Colonic Neoplasms; Humans; Reactive Oxygen Species