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Oncol Lett. 2017 Mar;13(3):1563-1568. doi: 10.3892/ol.2017.5651. Epub 2017 Jan 25.

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

Author information

1
Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang 310018, P.R. China.
2
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai 200031, P.R. China.
3
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

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.

KEYWORDS:

A549 sphere cells; apoptosis; cell cycle arrest; lung cancer-stem like cells; thioridazine

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