Naturally occurring lignans efficiently induce apoptosis in colorectal tumor cells

Plant-derived lignans caused cell loss by apoptosis in colorectal adenoma and carcinoma cells. Nordihydroguaiaretic acid (NDGA), commonly used for the inhibition of lipoxygenase isoenzymes, showed the strongest growth inhibition with an IC₅₀ of 1.9±0.5 µg followed by epiashantin (IC₅₀=9.8±4.5 µM) and arctigenin (IC₅₀=16.5±8.5 µM). The lignans caused a time- and dose-dependent loss of mitochondrial membrane potential (MMP), down regulation of the anti-apoptotic protein bcl_xl and an increase of the apoptotic index. The time interval until loss of MMP and down modulation of bcl_xl became evident correlated with the efficiency of growth inhibition by NDGA, epiashantin and yangambin. Bcl₂ and caspase 3 were not involved. NDGA also induced a shift of the culture population to the G₂/M phase of the cell cycle. With respect to these results, naturally occurring lignans could be useful in the therapy and chemoprevention of colorectal tumors.