K9(C4H4FN2O2)2Nd(PW11O39)2·25H2O induces apoptosis in human lung cancer A549 cells

K9(C4H4FN2O2)2Nd(PW11O39)2·25H2O诱导人肺癌A549细胞凋亡

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作者:Rong-Yao Xia, Ran-Ran Zhang, Zhe Jiang, Ya-Jiao Sun, Jing Liu, Fu-Hui Chen

Abstract

Lung cancer is the leading cause of cancer-associated mortality worldwide. The present study investigated the effects of K9(C4H4FN2O2)2Nd(PW11O39)2·25H2O (FNdPW), a chemically synthesized polyoxometalate that contains rare earth elements, on lung cancer growth, and explored the mechanism underlying its actions. The effects of FNdPW on the cell viability and apoptosis of human lung cancer A549 cells were measured using MTT assay, acridine orange/ethidium bromide staining and electron microscopy. The expression of apoptosis-related proteins, including B-cell lymphoma (Bcl)-2-associated death promoter (Bad), phosphorylated (p)-Bad, X-linked inhibitor of apoptosis (XIAP), apoptosis-inducing factor (AIF), Bcl-2-associated X protein (Bax) and Bcl-2, was determined by western blotting. Caspase-3 activity was measured using a caspase-3 activity kit. After 72 h of incubation, FNdPW reduced cell viability and induced apoptosis in A549 cells in a concentration- and time-dependent manner. FNdPW upregulated the pro-apoptotic Bad and Bax proteins, and downregulated the anti-apoptotic p-Bad, Bcl-2 and XIAP proteins. Furthermore, FNdPW also enhanced caspase-3 activity and increased the protein level of AIF in A549 cells, which was independent of the caspase-3 pathway. These events were associated with the regulation exerted by FNdPW on multiple targets involved in A549 cell proliferation. Therefore, FNdPW may be a novel drug for the treatment of lung cancer.

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