Repurposing phenothiazines for cancer therapy: compromising membrane integrity in cancer cells.
annexins
cancer treatment
membrane biophysical properties
membrane integrity
membrane repair
phenothiazines
plasma membrane
repurposing
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2023
2023
Historique:
received:
12
10
2023
accepted:
30
10
2023
medline:
11
12
2023
pubmed:
11
12
2023
entrez:
11
12
2023
Statut:
epublish
Résumé
The limitations of current cancer therapies, including the increasing prevalence of multidrug resistance, underscore the urgency for more effective treatments. One promising avenue lies in the repurposing of existing drugs. This review explores the impact of phenothiazines, primarily used as antipsychotic agents, on key mechanisms driving tumor growth and metastasis. The cationic and amphiphilic nature of phenothiazines allows interaction with the lipid bilayer of cellular membranes, resulting in alterations in lipid composition, modulation of calcium channels, fluidity, thinning, and integrity of the plasma membrane. This is especially significant in the setting of increased metabolic activity, a higher proliferative rate, and the invasiveness of cancer cells, which often rely on plasma membrane repair. Therefore, properties of phenothiazines such as compromising plasma membrane integrity and repair, disturbing calcium regulation, inducing cytosolic K-RAS accumulation, and sphingomyelin accumulation in the plasma membrane might counteract multidrug resistance by sensitizing cancer cells to membrane damage and chemotherapy. This review outlines a comprehensive overview of the mechanisms driving the anticancer activities of phenothiazines derivates such as trifluoperazine, prochlorperazine, chlorpromazine, promethazine, thioridazine, and fluphenazine. The repurposing potential of phenothiazines paves the way for novel approaches to improve future cancer treatment.
Identifiants
pubmed: 38074670
doi: 10.3389/fonc.2023.1320621
pmc: PMC10701681
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
1320621Informations de copyright
Copyright © 2023 Mehrabi, Elmi and Nylandsted.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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