B36 Effects of Trifluoperazine and Its Analog on A549 Human Lung Cancer Cells

Abstract

Although there have been great advances in technology, molecular diagnosis, and therapeutics, lung cancer is still the leading cause of cancer-related mortality all over the world. Recently, some antipsychotic drugs have been shown to possess anticancer activity. Thus, the present study was designed to evaluate the anticancer effects of trifluoperazine (TFP), a commonly used antipsychotic drug, and its synthetic analogs on human lung cancer cell lines. To this end, effects of TFP and its selected analog on A549 cells were investigated in in vitro as well as in vivo experiments. Synthetic TFP analogs were evaluated by the proliferation of A549 cells following drug treatment and compared to TFP. 3dc, a selected TFP analog, significantly inhibited the proliferation of A549 cells. Further experiment showed that TFP and 3dc had activities to inhibit the anchorage dependent/independent colony formation, and migration of A549 cells. Western blot analysis revealed that 3dc affected the gene expression levels related to apoptosis and cell cycle. Flow cytometric analysis showed that 3dc induced sub-G1 and G1 population and reduced cell population in S and G2/M phase. Additionally, Annexin V/PI staining showed that 3dc increased apoptotic cell population. Moreover, 3dc increased DNA fragmentation. 3dc showed stronger anticancer effects in all the experiments than TFP. In addition, in in vivo experimental models, 3dc also showed powerful anticancer effect in orthotropic lung cancer development than TFP. Thus, the present study demonstrates that a synthetic TFP analog has anti-lung cancer activity and provides a potential therapeutic candidate for lung cancer.