Thioridazine has potent antitumor effects on lung cancer stem-like cells

Abstract

Thioridazine (TDZ), originally an anti-psychotic drug, suppresses several types of cancer and has specificity for leukemia stem cells. The present study was performed to assess its effect on lung cancer stem-like cells, as its effect remains unknown. TDZ was utilized to treat lung cancer stem-like cells (A549 sphere cells) and its cytotoxic effect and mechanism were evaluated in vitro and in vivo. TDZ elicited cytotoxicity in A549 sphere cells and inhibited their proliferation in a dose-dependent pattern. A549 sphere cells treated with TDZ showed nuclear fragmentation, increased G0/G1 phase distribution, positive Annexin V staining, and a change in the expression of caspase family and cell cycle-associated proteins. These results suggest the induction of caspase-dependent apoptosis and cell cycle arrest. In addition, TDZ treatment resulted in significant inhibitory effect on mice xenografts established by A549 sphere cells. TDZ repressed growth of lung cancer stem-like cells in vitro and in vivo, indicating its potential application in targeting lung cancer stem-like cells.