Repurposing of antipsychotic agent trifluoperazine for multiple myeloma treatment: in vitro studies

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2016

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Ataş, Heval

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Multiple Myeloma (MM) is a hematological malignancy resulting from the proliferation of plasma B cells in the bone marrow. MM accounts for 20 % of deaths from blood cancers and 2 % of deaths from all cancers. Although there have been remarkable developments in the treatment of MM, it is still an incurable disease due to the drug resistance problem. Therefore, development of novel therapies is especially important for MM patients. Drug repurposing is one of the promising strategies to discover new anticancer agents. It considerably reduces the cost and time spent, and bypasses safety concerns necessary for de novo drug discovery. Trifluoperazine (TFP) is an FDA-approved antipsychotic drug mainly used in the treatment of schizophrenia. Apart from its fundamental antipsychotic effects, there are several studies showing its anticancer potential in various cancer types such as leukemia, lung, melanoma, prostate, and breast. The aim of this study was to investigate the anticancer potential and mechanism of TFP on U266 MM cell line. Firstly, dose and time dependent inhibitory and cytotoxic effect of TFP was studied. Then, three different apoptosis studies were performed. It was followed by cell cycle analysis to investigate its antiproliferative effect. Lastly, its combination potential with cisplatin was evaluated. TFP showed dose and time-dependent inhibitory and cytotoxic effect on U266 cell line. Its IC50 value was determined as 15.4 ± 0.7 μM. Caspase-3 and AnnexinV-PE / 7-AAD assays indicated apoptosis while JC-1 gave negative results. Cell cycle analysis showed that TFP did not induce cell cycle arrest in U266 cell line. TFP-cisplatin combination was additive with higher doses of TFP, and slightly antagonistic with lower doses of TFP. Based on these preliminary findings, TFP warrants further in-depth mechanistic studies and in vivo experiments to evaluate its therapeutic potential for MM treatment.

Subject Keywords

Trifluoperazine., Multiple myeloma., Antipsychotic drugs., Psychopharmacology.

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http://etd.lib.metu.edu.tr/upload/12620230/index.pdf
https://hdl.handle.net/11511/25866

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Graduate School of Natural and Applied Sciences, Thesis

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Citation Formats

H. Ataş, “Repurposing of antipsychotic agent trifluoperazine for multiple myeloma treatment: in vitro studies,” M.S. - Master of Science, Middle East Technical University, 2016.