Cytotoxicity of SH-SY5Y Neuroblastoma Cells to the Antipsychotic Drugs, Chlorpromazine and Trifluoperazine, is via a Ca2+ -Mediated Apoptosis Process and Differentiation of These Cells with Retinoic Acid Makes Them More Resistant to Cell Death

Cytotoxicity of SH-SY5Y Neuroblastoma Cells to the Antipsychotic Drugs, Chlorpromazine and Trifluoperazine, is via a Ca2+ -Mediated Apoptosis Process and Differentiation of These Cells with Retinoic Acid Makes Them More Resistant to Cell Death

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Corresponding Author
Francesco Mongelli
Thoracic Surgery, San Giovanni Hospital, Bellinzona, Switzerland

A B S T R A C T

Neuroblastomas usually occur in childhood and can have a relatively poor prognosis. Additionally, some antipsychotic drugs have been suggested to be neurotoxic, suggesting they might have therapeutic potential against neuronal cancer cells. In this study it was shown that 7 days treatment with 10 µM all-trans retinoic acid (ATRA) could alter SH-SY5Y (an undifferentiated neuroblastoma cell line) morphology in terms of neurite outgrowths and increased expression of the growth associated protein (GAP43), thus indicating that ATRA-treatment made these cells more differentiated in character. Next, a comparison of the effects of chlorpromazine and trifluoperazine, two types of typical first-generation antipsychotic drugs, on the cytotoxicity of both undifferentiated and ATRA-differentiated SH-SY5Y cells was undertaken. The results showed that both chlorpromazine and trifluoperazine, were highly cytotoxic to undifferentiated SH-SY5Y cells (LC50 values 5µM and 6µM, respectively). They were also deemed to be more selective towards neuronal cells compared to non-neuronal cells (COS7 cells). it was shown that cell death induced by chlorpromazine and trifluoperazine occurred mostly by Ca2+-mediated apoptosis. Furthermore, the cytotoxicity of chlorpromazine and trifluoperazine was decreased when the cells were differentiated with ATRA (LC50 values of 10.5µM and 12µM, respectively), indicating a possible therapeutic window for the potential use of chlorpromazine and trifluoperazine and potentially other FGAs in the treatment of neuroblastomas.

Article Info

Article Type
Research Article
Publication history
Received: Thu 23, Jan 2020
Accepted: Sat 15, Feb 2020
Published: Wed 19, Feb 2020
Copyright
© 2023 Francesco Mongelli. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Hosting by Science Repository.
DOI: 10.31487/j.COR.2020.02.03