Antipsychotic drug trifluoperazine as a potential therapeutic agent against nasopharyngeal carcinoma

Abstract

Background Trifluoperazine (TFP) is a typical antipsychotic primarily used to treat schizophrenia. In this study, we aimed to evaluate whether TFP can be used as a therapeutic agent against nasopharyngeal carcinoma (NPC) and identify its underlying molecular mechanisms. Methods We used NPC‐TW01, TW03, TW04, and BM to assess the anticancer effects of TFP by using cytotoxicity, wound healing, colony formation, and cell invasion assays. An in vivo animal study was conducted. RNA sequencing combined with Ingenuity Pathways Analysis was performed to identify the mechanism by which TFP influences NPC cells. Results Our data revealed that TFP decreased NPC cell viability in a dose‐dependent manner. The invasion and migration of NPC tumor cells were inhibited by TFP. An in vivo study also demonstrated the anticancer effects of TFP. RNA sequencing revealed several anticancer molecular mechanisms following TFP administration. Conclusions The antipsychotic drug TFP could be a potential therapeutic regimen for NPC treatment.

Synthesis and Structure of Novel Phenothiazine Derivatives, and Compound Prioritization via In Silico Target Search and Screening for Cytotoxic and Cholinesterase Modulatory Activities in Liver Cancer Cells and In Vivo in Zebrafish

“…Drug repurposing is the practice of utilizing clinically tested drugs in the market for alternative pathologies . Previous findings and published reviews have demonstrated the highly antiproliferative effects and therapeutic potential of antipsychotic phenothiazine (PTZ)-based drugs that act via different mechanisms including modulation of autophagy, membrane disruption/permeabilization, efflux pump inhibition, calcium overload, and/or other cell signaling pathways. − For instance, thioridazine selectively targets leukemia cancer stem cells of metastatic nature while halting cell cycle at G 0 / G 1 phase and prevents the migration of tumor cells . Haloperidol, fluphenazine, and flupentixol induce dose-dependent cell death in neuroblastoma and glioma cell lines , while perphenazine (PPH) has been shown to modulate negatively the cell cycle of SH-SY5Y neuroblastoma cell line .…”

Preparation and anti-tumor effects of mesoporous silica nanoparticles loaded with trifluoperazine

“…14 In recent years, studies have found that TFP has inhibitory effects on breast cancer, glioblastoma, lung cancer, etc. [15][16][17][18][19] TFP has also shown synergistic anti-cancer potential in combination with other anti-tumour drugs, exhibiting the ability to circumvent the multidrug resistance of cancer cells. [20][21][22][23][24] Since TFP has the tendency to cross the blood-brain barrier, it often has notable adverse effects on the central nervous system, such as drowsiness, dizziness and extrapyramidal reactions in patients, 25 which greatly affect its potential as an anti-cancer drug.…”