Caffeic Acid Phenethyl Ester Loaded in Microemulsions: Enhanced In Vitro Activity against Colon and Breast Cancer Cells and Possible Cellular Mechanisms
Caffeic acid phenethyl ester (CAPE) has high cytotoxicity against various cancer cells but has low water solubility and poor bioavailability. The objective of this work was to study a fully-dilutable oil-in-water microemulsion as a delivery vehicle of CAPE and the impacts on cellular uptake and expression of relevant proteins. Up to 3.30% w/w CAPE was dissolved in the microemulsion with droplets smaller than 20 nm and stable in 180 days. CAPE in the microemulsion had the significantly increased anti-proliferative activity against human HCT-116 colorectal and MCF-7 breast cancer cells than that in dimethyl sulfoxide. Dissolving CAPE in the microemulsion enhanced the cellular uptake according to fluorescence microscopy, flow cytometry, and HPLC. Subsequently, cyclin D1 was suppressed and p53 was induced, which regulated cell cycle and apoptosis, respectively, thereby enhancing anti-cancer activity. Findings from the present work suggest the potential of the studied microemulsion as a vehicle of CAPE for development of cancer intervention strategies.