This study investigated the anti-proliferative and apoptotic effect of flavonoids isolated from Korean
Citrus aurantium L. using A549 lung cancer cells. Flavonoids potently inhibited of A549 cells in a dosedependent
manner, whereas flavonoids had a weak inhibitory effect on proliferation of WI-38 cells. Flow
cytometry and Western blot analysis showed that flavonoids induced cell cycle arrest at the G2/M checkpoint
by controlling the proteins expression level of cyclin B1, cdc2, cdc25c and p21WAF1/CIP1. Also,
flavonoids induced apoptosis through the regulation of the expression of caspases, cleaved PARP and
Bax/Bcl-xL ratio. The activity of caspase-3 on A549 cells increased in a dose-dependent manner. These
results clearly indicated that the anti-cancer effect of flavonoids on A549 cells follows multiple cellular
pathways through G2/M arrest and the induction of apoptosis