Metabolism and Anticancer Activity of the Curcumin Analogue, Dimethoxycurcumin

Purpose: The plant-derived compound curcumin has shown promising abilities as a cancer chemoprevention and chemotherapy agent in vitro and in vivo but exhibits poor bioavailability. Therefore, there is a need to investigate modified curcumin congeners for improved anticancer activity and pharmacokinetic properties. Experimental Design: The synthetic curcumin analogue dimethoxycurcumin was compared with curcumin for ability to inhibit proliferation and apoptosis of human HCT116 colon cancer cells in vitro by estimating the GI 50 and LC 50 values and detecting the extent of apoptosis by flow cytometry analysis of the cell cycle. Metabolic stability and/or identification of metabolites were evaluated by recently developed mass spectrometric approaches after incubation with mouse and human liver microsomes and cancer cells in vitro . Additionally, circulating levels of dimethoxycurcumin and curcumin were determined in mice following i.p. administration. Results: Dimethoxycurcumin is significantly more potent than curcumin in inhibiting proliferation and inducing apoptosis in HCT116 cells treated for 48 h. Nearly 100% of curcumin but