ArticleClinical & experimental metastasis2023
Repurposing fluphenazine to suppress melanoma brain, lung and bone metastasis by inducing G0/G1 cell cycle arrest and apoptosis and disrupting autophagic flux.
Article in Clinical & experimental metastasis, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 9 citations in OpenAlex.
- Novel copper-phenothiazine-amino acid complexes exhibit selective anticancer activity via induction of apoptosis and cell cycle arrest in HepG2 cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Article
- Unraveling the Enigma of Melanoma Brain Metastasis: New Molecular Insights and Therapeutic Directions.International journal of molecular sciences · 2026Review
- Phenothiazine Derivatives and Their Impact on the Apoptosis Processes: A Review.Journal of applied toxicology : JAT · 2026Review
- Repurposing neuroleptics: clozapine as a novel, adjuvant therapy for melanoma brain metastases.Clinical & experimental metastasis · 2025Article
- The anti-cancer efficacy of a novel phenothiazine derivative is independent of dopamine and serotonin receptor inhibition.Frontiers in oncology · 2023Article
- Repurposing phenothiazines for cancer therapy: compromising membrane integrity in cancer cells.Frontiers in oncology · 2023Review
- Therapeutic Mechanisms of Phenothiazine Drugs: A Mini-Review of Advances in Cancer Treatment and Antibiotic Resistance.Iranian journal of pharmaceutical research : IJPRReview
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brain metastasis is the main cause of treatment failure and melanoma-related death. Inadequate concentrations of therapeutic drugs in the brain due to the blood-brain barrier (BBB) pose a major challenge in the treatment of brain metastasis. Antipsychotics can cross the BBB to reach the brain. Fluphenazine (FPZ) inhibits the survival of melanoma cells in vitro. However, its efficacy in suppressing the metastasis of melanoma, especially brain metastasis, remains unknown. Therefore, we explored whether fluphenazine (FPZ) can be repurposed for treating melanoma metastasis. A subcutaneous tumor model, and experimental metastasis models that simulate the outgrowth of melanoma cells in the brain, lung, and bone were established to verify the inhibitory effect of FPZ on melanoma cells. FPZ showed potential inhibitory effects against melanoma both in vivo and in vitro. It induced G0/G1 phase arrest and-mitochondrion-mediated intrinsic apoptosis, and inhibited autophagic flux in melanoma cells in vitro. In vivo, subcutaneous tumor, brain, lung, and bone models of metastatic melanoma were established. Intraperitoneal injection of FPZ (8 mg/kg) significantly inhibited melanoma growth in the subcutaneous and experimental metastasis models. In a lung metastasis model, FPZ reduced the proportion of M2 macrophages and increased the proportion of CD8
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Registered trials
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