Polyamine analogue CPENSpm inhibits proliferation of human lung cancer cells by interfering polyamine metabolism / 中国药理学通报

ABSTRACT

Aim To study the effects of polyamine analogue CPENSpm on the human lung cancer line A549 in cell proliferation and apoptosis.Methods MTS was used to assay the cell proliferation,chemical analysis methods were used to determine the activities of enzymes in the polyamine metabolism,HPLC was performed to assay the intracellular concentration of polyamines,Sub-G1 and DNA fragmentation assays were used to determine the cell apoptosis.Results Treating A549 lung cancer cells by CPENSpm resulted in①cell-growth inhibition and cell apoptosis;②inhibition of ODC(key enzyme in polyamine synthetic pathway)and activation of SSAT and SMO(key enzymes in polyamine catabolism);③great decrease of intracellular polyamine concentrations.MDL72527,the SMO inhibitor,can antagonize the effect of CPENSpm on inhibiting the proliferation of A549 cells.Conclusion CPENSpm inhibits proliferation and induces apoptosis of human A549 lung cancer cell line by interfering the polyamine metabolism,depleting intracellular polyamine contents that are need by quick-growth of cancer cells and inducing production of H2O2.