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

Download

index.pdf

Date

2016

Author

Ataş, Heval

Metadata

Show full item record

Item Usage Stats

208
views

72
downloads

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.

URI

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

Collections

Graduate School of Natural and Applied Sciences, Thesis

Suggestions

OpenMETU
Core

Anti-cancer effect of clofazimine as a single agent and in combination with cisplatin on U266 multiple myeloma cell line Durusu, Ipek Z.; Husnugil, Hazal H.; ATAŞ, Heval; BİBER, Aysenur; GEREKCİ, Selin; Gulec, Ezgi A.; Özen, Can (2017-04-01) Multiple Myeloma (MM) is a malignant neoplasm of bone marrow plasma B cells with high morbidity. Clofazimine (CLF) is an FDA-approved leprostatic, anti-tuberculosis, and anti-inflammatory drug that was previously shown to have growth suppression effect on various cancer types such as hepatocellular, lung, cervix, esophageal, colon, and breast cancer as well as melanoma, neuroblastoma, and leukemia. The objective of this study was to evaluate the anticancer effect and mechanism of CLF on U266 MM cell line. C...
Anticancer effect and combination potential of clofazimine in multiple myeloma Durusu, İpek Zeynep; Özen, Can; Gündüz, Ufuk; Department of Biotechnology (2016) Multiple Myeloma (MM) is a malignant neoplasm of bone marrow plasma B cells with high low survival rates. Clofazimine (CLF) is a FDA-approved leprostatic, anti-tuberculous and anti-inflammatory drug. CLF has shown to have growth suppression in various cancers such as hepatocellular, lung, cervix, melanoma, esophageal, colon, leukemia, neuroblastoma and breast. Objective of this study was to investigate anticancer effect and mechanism of Clofazimine on U266 Multiple Myeloma cell line. The relative cell viabi...
Induction of apoptosis and cell cycle arrest on U266 multiple myeloma cell line by prochlorperazine Hüsnügil, Hepşen Hazal; Özen, Can; Banerjee, Sreeparna; Department of Biochemistry (2016) Multiple myeloma (MM) is a plasma cell neoplasm accounting for 1% of all malignancies and 13% of hematological malignancies. Despite the introduction of potent anticancer agents, MM remains as an incurable disease. High frequency of relapses and acquisition of resistance to current chemotherapy create a need for the development of novel agents for MM treatment. Prochlorperazine (PCP) is an FDA-approved phenothiazine drug, mainly used for the treatment of chemotherapy-associated nausea and vomiting. In addit...
Anticancer activity of chlorpromazine on U266 multiple myeloma cell line Güleç, Aliye Ezgi; Özen, Can; Özçubukçu, Salih; Department of Biochemistry (2017) 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 t...
Anti-Cancer Effects of Clofazimine As a Single Agent and in Combination with Cisplatin in Multiple Myeloma Durusu, Ipek; Hüsnügil, Hepşen Hazal; Atas, Heval; Biber, Aysenur; Gerekci, Selin; Gulec, Aliye Ezgi; Özen, Can (2016-12-02) Multiple Myeloma (MM) is a malignant neoplasm of bone marrow plasma B cells with high morbidity. Clofazimine (CLF) is an FDA-approved leprostatic, anti-tuberculosis, and anti-inflammatory drug that was previously shown to have growth suppression effect on various cancer types such as hepatocellular, lung, cervix, esophageal, colon, and breast cancer as well as melanoma, neuroblastoma, and leukemia. The objective of this study was to evaluate the anticancer effect and mechanism of CLF on U266 MM cell line. C...

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.