Apoptotic effects of bioactive fraction isolated from Glossogyne tenuifolia on A549 human lung cancer cells

Our previous study has demonstrated that the ethyl acetate (EA) extract of Glossogyne tenuifolia has strong cytotoxicity toward several human cancer cells including lung cancer cells. In this work, a bioactive fraction (Fr. C) that exhibited significant antiproliferative activity on A549 human lung cancer cells (IC50 = 18.2 μg/ml) and had less sensitive effect on MRC-5 normal lung fibroblast cells (IC50 = 34.4 μg/ml) was obtained from the column chromatographic fractionation of EA extract. Cytometric analysis results indicated that the A549 cells were arrested at the G0/G1 phase by treating this fraction. The Fr. C induced the apoptosis of A549 cells through the mitochondrial pathway by down-regulating Bcl-2 and Bcl-xL protein expression, up-regulating Bad and Bax protein expression and activating caspase-9 and caspase-3. From the GC-Mass spectrometric analysis, mokko lactone (4(15),10(14)-guaiadien-12,6-olide lactone), phytol (3,7,11,15-tetramethyl-2-hexadecen-1-ol), glossogin (1′-acetoxy-4-O-isovalyryleugenol), and dehydrocostus lactone (DL, 6-hydroxy-guaia-4(15),10(14),11(13)-trien-12-oic acid lactone) were the main components of Fr. C. The cytotoxic test demonstrated that DL (IC50 = 6.3 μg/ml), phytol (IC50 = 11.7 μg/ml) and glossogin (IC50 = 48.5 μg/ml) are the major ingredients responsible for most of the cytotoxic activity on A549 cells of Fr. C.