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

Jiani Shen1, Buyun Ma1, Xinmin Zhang1

  • 1Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang 310018, P.R. China.

Oncology Letters
|April 30, 2017
PubMed

Insights

The anti-psychotic drug Thioridazine (TDZ) effectively suppressed lung cancer stem-like cells in laboratory and animal studies. TDZ demonstrated potential for targeting these aggressive cancer cells through apoptosis and cell cycle arrest.

Area of Science:

  • Oncology
  • Pharmacology
  • Cancer Stem Cell Biology

Background:

  • Thioridazine (TDZ), an antipsychotic, exhibits anticancer properties, particularly against leukemia stem cells.
  • The therapeutic potential of TDZ against lung cancer stem-like cells remains unexplored.

Purpose of the Study:

  • To investigate the efficacy of Thioridazine (TDZ) in targeting lung cancer stem-like cells.
  • To elucidate the cytotoxic mechanisms of TDZ in lung cancer stem-like cells both in vitro and in vivo.

Main Methods:

  • Lung cancer stem-like cells (A549 sphere cells) were treated with TDZ.
  • Cytotoxicity, proliferation, apoptosis (Annexin V staining, caspase activation), cell cycle distribution, and protein expression were analyzed.
  • In vivo efficacy was assessed using mouse xenograft models.

Main Results:

  • TDZ induced dose-dependent cytotoxicity and inhibited proliferation of A549 sphere cells.
  • TDZ triggered apoptosis via caspase activation and induced G0/G1 cell cycle arrest.
  • TDZ significantly inhibited tumor growth in vivo in xenograft models.

Conclusions:

  • TDZ exhibits potent anti-cancer activity against lung cancer stem-like cells.
  • The mechanism involves caspase-dependent apoptosis and cell cycle arrest.
  • TDZ shows promise as a therapeutic agent for targeting lung cancer stem-like cells.
Keywords:
A549 sphere cellsapoptosiscell cycle arrestlung cancer-stem like cellsthioridazine

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