Trifluoperazine (TFP) is an antagonist against dopamine receptors, act as antipsychotic agent and is widely used to treat schizophrenia or related psychoses [1,2]. Trifluoperazine is also a well-known calmodulin antagonist [3].
Trifluoperazine significantly restricted the invasion of glioblastoma cells at a concentration higher than 1 µmol/L, with a half-maximal effective concentration at around 10 µmol/L on invasion of U87MG cells by performing Matrigel transwell invasion assay. The ratio of proliferated glioblastoma cells was significantly decreased in TFP-treated cells [4]. Trifluoperazine inhibits cell vitality, proliferation, and induces cell apoptosis of HCT116 cells with IC50 =14 µM [3]. Trifluoperazine (30 µM, 24h) induced pancreatic adenocarcinoma (PDAC) MiaPaCa-2 cell death and decreased in intracellular availability of ATP [5].
Trifluoperazine (5 mg/kg/day) significantly suppressed the glioblastoma growth of the xenograft mice as evidenced by a marked decrease of glioblastoma tumor size in TFP-treated mice at day 21, there was no lung metastasis in TFP-treated group in the skin xenograft model [4]. Administration of TFP induced remarkably tumor regression with decreased tumor volume in the xenograft model of human HCT116 [3]. Trifluoperazine binds and mimics the effect of the genetic inhibition of NUPR1, a stress protein that promotes tumor growth and acts as a strong anticancer drug in vitro and in vivo in xenografted nude mice [6].
References:
[1]. de Oliveira Marques L, Soares B, de Lima M S. Trifluoperazine for schizophrenia[J]. Cochrane Database of Systematic Reviews, 2004 (1).
[2]. Hong M, Jenner P, Marsden C D. Comparison of the acute actions of amine-depleting drugs and dopamine receptor antagonists on dopamine function in the brain in rats[J]. Neuropharmacology, 1987, 26(2-3): 237-245.
[3]. Qian K, Sun L, Zhou G, et al. Trifluoperazine as an alternative strategy for the inhibition of tumor growth of colorectal cancer[J]. Journal of cellular biochemistry, 2019, 120(9): 15756-15765.
[4]. Kang S, Hong J, Lee J M, et al. Trifluoperazine, a well-known antipsychotic, inhibits glioblastoma invasion by binding to calmodulin and disinhibiting calcium release channel IP3R[J]. Molecular cancer therapeutics, 2017, 16(1): 217-227.
[5]. Huang C, Lan W, Fraunhoffer N, et al. Dissecting the anticancer mechanism of trifluoperazine on pancreatic ductal adenocarcinoma[J]. Cancers, 2019, 11(12): 1869.
[6]. Neira J L, Bintz J, Arruebo M, et al. Identification of a drug targeting an intrinsically disordered protein involved in pancreatic adenocarcinoma[J]. Scientific reports, 2017, 7(1): 1-15.