Naringenin sensitizes lung cancer NCI-H23 cells to radiation by downregulation of akt expression and metastasis while promoting apoptosis

摘要

Background: Naringenin (NGN) isaflavonoid that has shown anticanceractivities, but theability ofNGN to radiosensitizecells ofthe non-smallcell variety oflung cancer has not been looked into yet. Objectives: The objective ofthestudywas to check for theability ofNGN to promoteradiosensitization ofthelung cancercell line – NCI-H23 (H23). Materials andMethods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromideassay, trypan blueexclusion assay,and colonyforming assaywere performed to check theeffect ofNGN, with and without X-ray treatment, on the viability ofcancercells. Protein carbonylation, DNA fragmentation,and caspase-3 activitywere determined. Thelevels of pAkt, Akt, matrixmetalloproteinase-2 (MMP-2), RAD50,and p21 proteins werelooked at by Western blotting. Messenger RNA(mRNA) levels ofAKT1, CASPASE3, BAX, BCL2,and BCLXLwerealso checked. Results: When combined with radiation, NGN lowered thesurvivability ofH23 cells. NGN showed a prooxidanteffect while no DNAfragmentationwas observed. mRNAlevels ofCASPASE3 and caspase-3 activity also showed an increase. pAkt, Akt, MMP-2,and p21 protein levels werelowered in the NGN-treated groups, whilethe RAD50 protein levels showed an increase. The mRNAlevels ofBCL2 and BCLXLwerelowered, while BAXmRNAlevels wereelevated in responseto NGN treatment. Conclusion: Theresults showed that NGN, used singularly or in combinationwith radiation,can lower the procancerousand prometastatic Akt, p21,and MMP-2 proteins while upregulating theapoptotic process.