Apoptosis in human lung adenocarcinoma cell line A549 by derivative of podophyllotoxin

    ZHANG Huiª²Fang, ZHANG Xu, FAN Linª²Lan

    Room of Electron Microscope, Medical Experimental Center, Lanzhou University, Lanzhou 730000, China

    ¡¾Abstract¡¿ AIM: To study the apoptosis of human lung adenocarcinoma A549 cells induced by CNª²2, a derivative of podophyllotoxin, and to obtain insights into its molecular mechanism of action. METHODS: MTT assay, electron microscopy, DNA agarose gel electrophoresis and cell cycle ananlysis were used to examine apoptosis in A549 cells. Expressions of Bclª²2, caspase 3 and Fas proteins were measured with flow cytometry. RESULTS: CNª²2 was demonstrated to exert antiproliferative activity in a doseª² and timeª²dependent manner. IC50 of A549 after 24, 48, 72 h exposure to CNª²2 was 108.20, 41.28, 20.67 mg/L, respectively. Typical apoptotic morphological changes were observed by electron microscope; agarose gel electrophoresis showed an evident DNA fragmentation; cell cycle analysis indicated an increased S phase proportion,as well as an apparent S/G2 phase arrest. CNª²2 decreased Bclª²2 protein expression (P<0.05) dramatically . Fas protein expression showed no obvious changes. CONCLUSION: CNª²2 could inhibit the growth of A549 cells via the induction of S/G2ª²phase arrest, which is probably associated with the decreased Bclª²2 expression and cell cycle arrest. ......