A potential anticancer agent 1,2-di(quinazolin-4-yl)diselane induces apoptosis in non-small-cell lung cancer A549 cells

摘要

Lung cancer is presently the most commonly diagnosed metastatic tumor and the leading cause of cancer-related deaths worldwide. Moreover, drug resistance occurs frequently in lung cancer patients. There is an urgent need for developing promising anticancer drugs to improve overall survival of patients with lung cancer. In our recent antitumor drug discovery study, 1,2-di(quinazolin-4-yl)diselane (LG003) exhibited broad spectrum antitumor effects, and demonstrated such effect on A549 cells through physiological pathways rather than cytotoxicity. This suggests that compound LG003 is a potential antitumor agent. In the present study, treatment time and dosage tests indicated LG003 inhibited A549 cells in time- and dosage-dependent manner. Morphological observation did show that compound LG003 treatment resulted in inhibition of cell proliferation and morphological changes in time- and dosage-dependent manner. Subsequent cell cycle analysis revealed that LG003-induced G1-phase arrest followed by accumulation in hypodiploid population phase in cell cycle progression. The typical apoptosis-like morphological changes were also observed in synchronous observation of A549 cells. AO/EB staining and DNA ladder assay confirmed LG003-induced nuclear condensation and characteristic apoptotic DNA ladder in A549 cells. Annexin V-FITC apoptosis analysis indicated that LG003 treatment for 48 h induced the apoptosis of A549 cells in a dosage-dependent manner. Based on these results, we concluded that LG003 executed antitumor activity mainly through inhibiting cell proliferation in the early stage of treatment, then inducing apoptotic death which implied that LG003 should be a potential antitumor candidate worthing more extensive study to be developed as anticancer agents against Lung cancer.