Anticancer activity of chlorpromazine on U266 multiple myeloma cell line

Date

2017

Author

Güleç, Aliye Ezgi

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Multiple Myeloma (MM) is the second most common hematological malignancy caused by malignant growth of plasma B cells. It accounts for 10% of deaths from blood cancers. Although introduction of new drugs has significantly increased the success of chemotherapy, MM remains as an incurable disease with a high relapse rate. Drug repositioning, finding new uses for approved drugs, is a frequently used strategy for the discovery of new chemotherapeutic agents. Since already approved drugs are used, the cost and time spent are considerably reduced. Chlorpromazine (CPZ), which has been used in several drug repositioning studies against different cancer types, is an FDA-approved antipsychotic drug mainly used in the treatment of schizophrenia. In this work, we aim to investigate the anticancer effect and mechanism of CPZ on U266 MM cell line. Firstly, CPZ`s in vitro inhibitory effect at various doses and time points was studied. Then three different apoptosis studies and cell cycle analysis were conducted. Combination potential of CPZ with cisplatin was also investigated during this study. CPZ showed both dose- and time- dependent growth inhibitory effect on U266 MM cell line with an IC50 value of 22.4 ± 0.9 μM. Apoptotic effect of CPZ was indicated by activation of Caspase-3 and change in the cell membrane asymmetry. In addition, CPZ treatment induced cell cycle arrest at G2/M phase. Its combination with cisplatin was moderately synergistic. Based on our preliminary findings, therapeutic potential of CPZ for MM treatment can be investigated with in-depth mechanistic studies and in vivo experiments..

Subject Keywords

Cell lines., Apoptosis., Chlorpromazine., Drug development., Drugs, Cancer

URI

http://etd.lib.metu.edu.tr/upload/12621303/index.pdff
https://hdl.handle.net/11511/26646

Collections

Graduate School of Natural and Applied Sciences, Thesis

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Citation Formats

A. E. Güleç, “Anticancer activity of chlorpromazine on U266 multiple myeloma cell line,” M.S. - Master of Science, Middle East Technical University, 2017.