Induction of Apoptosis by Eurycoma longifolia Jack Extracts

Abstract

Extracts of the plant Eurycoma longifolia have been shown to possess cytotoxic, antimalarial, anti-ulcer, antipyretic and plant growth inhibition activities. The present study investigated the effects of extracts and their chromatographic fractions from the root of E. longifolia on the growth of a human breast cancer cell line, MCF-7. Our data indicated that E. longifolia extracts and fractions exert a direct antiproliferative activity on MCF-7. The bioassay-guided root fractionation resulted in the isolation of three active fractions, F5, F6 and F7, which displayed IC₅₀ values of (6.17±0.38) μg/ml, (4.40±0.42) μg/ml and (20.00±0.08) μg/ml, respectively. The resultant from F7 purification, F16, exhibited a higher cytotoxic activity towards MCF-7, (IC₅₀=15.23± 0.66 μg/ml) and a certain degree of selectivity against a normal breast cell line, MCF-10A (IC₅₀=66.31±0.47 μg/ml). F16 significantly increased apoptosis in MCF-7 cells, as evaluated by the Tdt-mediated dUTP nick end labelling assay and nuclear morphology. Western blotting revealed down-regulation of the anti-apoptotic Bcl-2 protein expression. F16, however, did not affect the expression of the pro-apoptotic protein, Bax. These results, therefore, suggest that F16 has antiproliferative effects on MCF-7 cells by inducing apoptosis through the modulation of Bcl-2 protein levels.