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Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
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Trifluoperazine exerts anti-osteosarcoma effect by inducing mitochondria-dependent apoptosis via AKT/TXNIP signaling

Xiangchen Zeng1, Wenkai Chen1, Naichun Yu2

  • 1School of Medicine, Xiamen University, Xiamen, China.

Toxicology and Applied Pharmacology
|August 31, 2024
PubMed

Insights

Trifluoperazine (TFP), an antipsychotic, shows promise in treating osteosarcoma (OS). It inhibits OS cell growth and migration by increasing reactive oxygen species (ROS) and inducing apoptosis, offering a potential new therapy.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Osteosarcoma (OS) survival rates have not improved in decades, necessitating novel therapeutic strategies.
  • Trifluoperazine (TFP), an existing antipsychotic, demonstrates anticancer properties against various tumors.
  • The specific mechanisms of TFP action in osteosarcoma remain largely unelucidated.

Purpose of the Study:

  • To investigate the molecular pathways and therapeutic potential of trifluoperazine (TFP) in osteosarcoma (OS).
  • To determine TFP's effects on OS cell behavior, cell cycle, and apoptosis.
  • To explore the relationship between TFP, reactive oxygen species (ROS), thioredoxin binding protein (TXNIP), and AKT signaling in OS.

Main Methods:

  • Cell culture experiments assessing OS cell migration, proliferation, and cell cycle arrest.
  • RNA-sequencing (RNA-Seq) to analyze gene expression changes induced by TFP.
  • Investigation of reactive oxygen species (ROS) production and mitochondrial apoptosis pathways.
  • Western blot analysis to examine protein expression and phosphorylation, particularly of AKT and TXNIP.

Main Results:

  • TFP significantly inhibited OS cell migration and proliferation, inducing G0/G1 cell cycle arrest.
  • TFP elevated thioredoxin binding protein (TXNIP) expression, leading to increased reactive oxygen species (ROS) production and mitochondria-dependent apoptosis.
  • AKT dephosphorylation was identified as an upstream event promoting TXNIP expression, revealing a novel regulatory axis.
  • In vivo studies confirmed TFP's efficacy in suppressing OS tumor growth and inducing apoptosis with minimal side effects.

Conclusions:

  • Trifluoperazine (TFP) exerts anticancer effects in osteosarcoma by modulating the TXNIP/ROS/apoptosis pathway and regulating AKT signaling.
  • TFP demonstrates significant potential as a therapeutic agent for osteosarcoma, warranting further clinical investigation.
  • The findings provide a deeper understanding of TFP's anticancer mechanisms and its potential application in OS treatment.
Keywords:
AKT/TXNIPMitochondria-Dependent ApoptosisOsteosarcomaTrifluoperazine

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