Francesco  Mongelli,Israa J. Hakeem ,Nikolas J Hodges ,
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
Clinical Oncology and Research
2020
2613-4942
http://dx.doi.org/10.31487/j.COR.2020.02.03
https://www.sciencerepository.org/cytotoxicity-of-sh-sy5y-neuroblastoma-cells-to-the-antipsychotic-drugs_COR-2020-2-103 
Abstract: 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.Keywords: Antipsychotic drugs, chlorpromazine, trifluoperazine, SH-SY5Y cells, retinoic acid, differentiated