Luteolin induced G2 phase cell cycle arrest and apoptosis on non-small cell lung cancer cells

In this study, we investigated the underlying molecular mechanism for the potent cell cycle inhibition and pro-apoptotic effect of luteolin (2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-chromenone) on human non-small-cell lung carcinoma cell line A549. MIT assay showed that luteolin had obvious cytotoxicity on A549 with IC50 of 40.2 mu M at 48 h. Pro-apoptotic effect of luteolin on A549 cells was demonstrated by Hoechst 33258 staining assay and annexin V-FITC/PI double staining analysis. A great quantity of apoptotic cells and increasing G2 phase cells were observed by flow cytometry. Western blotting assay revealed that luteolin activated JNK, increased Bax, promoted procaspase-9 cleavage and activated caspase-3 at last. Assay using TNF alpha, an active agent of NF-kappa B, showed that pretreatment of A549 cells with luteolin could inhibit TNFa induced trans-nuclear of NF-kappa B. In summary, luteolin displayed a significant cytotoxic effect through cell cycle arrest and apoptosis induction in A549 cells. Pro-apoptotic effect was implemented via activating JNK and inhibiting translocation of NF-kappa B (p65). These results suggested that luteolin might have therapeutic potential against NSCLC. (C) 2011 Elsevier Ltd. All rights reserved.