Thioridazine, an antipsychotic drug, elicits potent antitumor effects in gastric cancer

Mu,Jiasheng; Xu,Haineng; Yang,Yu; Huang,Weidan; Xiao,Jing; Li,Maolan; Tan,Zhujun; Ding,Qichen; Zhang,Lin; Lu,Jianhua; Wu,Xiangsong; Liu,Yingbin

doi:10.3892/or.2014.3068

Thioridazine, an antipsychotic drug, elicits potent antitumor effects in gastric cancer

Authors:
- Jiasheng Mu
- Haineng Xu
- Yu Yang
- Weidan Huang
- Jing Xiao
- Maolan Li
- Zhujun Tan
- Qichen Ding
- Lin Zhang
- Jianhua Lu
- Xiangsong Wu
- Yingbin Liu
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Affiliations: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University school of Medicine, Shanghai 200092, P.R. China, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China, College of Life Science, Henan Normal University, Xinxiang, Henan 453007, P.R. China
Published online on: March 6, 2014 https://doi.org/10.3892/or.2014.3068
Pages: 2107-2114

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Abstract

Thioridazine, an antipsychotic drug, has been reported to induce apoptosis in various types of cancer cells, with specificity on targeting cancer stem cells (CSCs). However, whether it elicits anticancer effects in gastric cancer has never been reported. In the present study, we examined the ability of thioridazine to induce cell death in the gastric cancer cell lines NCI-N87 and AGS, and detected its in vivo tumor inhibition capacity. Thioridazine elicited cytotoxic effects on NCI-N87 and AGS cells in a dose-dependent manner, and inhibited the colony formation abilitiy of the NCI-N87 and AGS cells. Thioridazine treatment induced nuclear fragmentation, increased the proportion of sub-G1 phase cells, and elevated the percentage of Annexin V-positive cells, suggesting the occurrence of apoptosis. Moreover, thioridazine induced gastric cancer cell apoptosis in a caspase-dependent manner, as shown by a decrease in the precursors of casapse-9, caspase-8 and caspase-3, and by the ability of the caspase inhibitor Z-VAD-FMK to reverse the cytotoxic effect of thioridazine. JC-1 staining further revealed that thioridazine induced gastric cancer cell apoptosis via the mitochondrial pathway. In addition, thioridazine pretreatment inhibited the growth of NCI-N87 cell-derived tumors. The present study demonstrated that the antipsychotic drug thioridazine possesses anti-gastric cancer ability through in vitro and in vivo experiments, suggesting thioridazine as a potential drug in gastric cancer therapy.

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