Luteolin Triggers Mitochondria-dependent Apoptosis And Inhibits The Proliferation Of A549Cell Lines

Objective:To explore the effects of luteolin on the proliferation and apoptosis of humanlung adenocarcinoma A549cells, and the underlying molecular mechanism.Methods:The proliferation inhibition of A549cells were evaluated as by MTT assay andcloning formation test. DNA ploidy and the early apoptotic cell percentage werecalculated by flow cytometry. The expressions of Bax, Bcl-2, Bcl-XL, Mcl-1,Caspase-9, Caspase-3, PARP and GAPDH were analyzed by Western blot. Themembrane potential of mitochondria (△ψm) was detected by Mitochondrialmembrane potential assay kit with JC-1.Results:After treated with luteolin for48h at concentration0μmol/L,20μmol/L,40 μmol/L,80μmol/L,120μmol/L, Compared with control group, DMSO controlgroup, the inhibition of proliferation effects of A549cells treated with luteolinwere significantly inhibited (P<0.05). The IC50value was80.0μM. These resultsindicated that luteolin can inhibited the proliferation of A549cell in a dosedependent manner. But it is no use for L-02cells. The clone formation of A549cells treated with luteolin was significantly inhibited (P<0.05). DNA flowcytometric analysis indicated that Luteolin induced a S phase arrest of the cellcycle. Percentages of early apoptosis rates was significantly higher in a dosedependent manner in luteolin treatment groups than those in the control group, Cellmembrane potential of mitochondria (△ψm) was decreased. The expression ofBcl-xl, Bcl-2, Caspase-9, Caspase-3and PARP was decreased, while that of Mcl-1was not affected. And Bax was increased after treated with luteolin.Conclusion:Luteolin exhibited an anti-proliferative effect in A549cells in a dose dependentmanner, Luteolin induced a S phase arrest of the cell cycle. Annexin V-PI stainingshowed that luteolin could increase the percentage of early apoptosis rates. Thesemeans luteolin exhibits an anti-proliferative effect in A549cells by inducingcell apoptosis.A549cells treated with luteolin, the membrane potential of mitochondria (△ψm) was decreased and the expression of Bcl-2family proteins were changed, andthe expression of Caspase9, Caspase3and PARP were also decreased. Indicatsthat mitochondria-dependent apoptosis was involved in the apoptosis of A549cells.