Update on the bioavailability and chemopreventative mechanisms of dietary chlorophyll derivatives

Chlorophyll, a phytochemical responsible for the green pigmentation in plants, has been studied for almost 100 years for its biological activities in humans. Over the past 30 years, the potential chemopreventative activities of both natural chlorophylls and their processed induced derivatives as well as the semisynthetic forms, such as sodium copper chlorophyllin, have been the focus of many research efforts. Established as potential chemopreventative agents with little to no bioavailability themselves, the activities of chlorophyll derivatives were generally ascribed to their ability to modulate mutagen/carcinogen bioavailability, their metabolism, and ultimately their ability to decrease the "exposure" to these carcinogens for humans at risk. More recently, systemic activities of chlorophyll derivatives have been reported to include modulation of oxidative stress and regulation of xenobiotic metabolizing systems and gene expression of systems critical to prevention of initiation and/or progression of cancer including NFE2-related factor 2, nuclear factor kappa B, TGF-β, and β-catenin pathways. With this in mind, the goals of this review are to provide an update to the comprehensive review of Ferruzzi and Blakeslee (2007) to include new insights into the behavior of chlorophyll derivatives in the gut as well as evidence of the systemic bioavailability of chlorophyll derivatives and their metabolites in support of potential impacts in prevention of cancer throughout the body.