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Neuroblastomas usually occur in childhood and can have a relatively poor prognosis. Additionally, someantipsychotic drugs have been suggested to be neurotoxic, suggesting they might have therapeutic potentialagainst neuronal cancer cells. In this study it was shown that 7 days treatment with 10 µM all-trans retinoicacid (ATRA) could alter SH-SY5Y (an undifferentiated neuroblastoma cell line) morphology in terms ofneurite outgrowths and increased expression of the growth associated protein (GAP43), thus indicating thatATRA-treatment made these cells more differentiated in character. Next, a comparison of the effects ofchlorpromazine and trifluoperazine, two types of typical first-generation antipsychotic drugs, on thecytotoxicity of both undifferentiated and ATRA-differentiated SH-SY5Y cells was undertaken. The resultsshowed that both chlorpromazine and trifluoperazine, were highly cytotoxic to undifferentiated SH-SY5Ycells (LC50 values 5µM and 6µM, respectively). They were also deemed to be more selective towardsneuronal cells compared to non-neuronal cells (COS7 cells). it was shown that cell death induced bychlorpromazine and trifluoperazine occurred mostly by Ca2+-mediated apoptosis. Furthermore, thecytotoxicity of chlorpromazine and trifluoperazine was decreased when the cells were differentiated withATRA (LC50 values of 10.5µM and 12µM, respectively), indicating a possible therapeutic window for thepotential use of chlorpromazine and trifluoperazine and potentially other FGAs in the treatment ofneuroblastomas.

clinical oncology and research

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