Study On The Mechanism Of Apoptosis Induced By 1,7-Bis(4-hydroxyphenyl)-1,4-heptadien-3-one In Lung Cancer Cells

PURPOSE:1,7-Bis(4-hydroxyphenyl)-1,4-heptadien-3-one(EB3 0)is a diarylheptanoid-like compound isolated from Viscum coloratum.This curcumin analog exhibits significant cytotoxic activity against HeLa,SGC-7901,and MCF-7 cells.However,little is known about the anticancer effects and mechanisms of EB30 in human lung cancer.In the current study,we estimated the effects of EB30 on human lung cancer A549 and NCI-H292 cells.METHODS:A CCK-8 assay and RTCA were used to identify the proliferation of EB30.To investigate the effect of EB30 on the cycle progression,lung cancer cells were stained with PI for 1 hour and analyzed using a FACS Calibur flow cytometer system.DAPI staining and an Annexin V-FITC/propidium iodide(PI)kit were used to validate that apoptosis contributed to the reduction in cell viability.JC-1 was used as a fluorescence probe to detect MMP.DCFH-DA was used to determine intracellular reactive oxygen species(ROS)levels.Western blot analysis was used to estimate the expression of apoptosis related proteins.RESULTS:The current study reports that EB30 significantly reduced the cell viability of A549 and NCI-H292 human lung cancer cells.Further examination revealed that EB30 not only induced cell cycle arrest and promoted the generation of ROS but also induced cell apoptosis through the intrinsic and extrinsic signaling pathways.Furthermore,EB30 upregulated the expression levels of p-ERK 1/2 and p-P90RSK,whereas downregulating the phosphorylation of Akt and P70RSK.Cell viability was further inhibited by the combination of EB30 with LY294002(a PI3K inhibitor)or U0126(a specific MEK inhibitor).CONCLUSION:The current study indicates that EB30 is a potential anticancer agent that induces cell apoptosis via suppression of the PI3K/Akt pathway and activation of the ERK1/2 pathway.