title: Anti-cancer effect of clofazimine as a single agent and in combination with cisplatin on U266 multiple myeloma cell line.
abstract: 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. CLF (10μM, 24h) treatment resulted up to 72% growth suppression on a panel of hematological cell lines. Dose-response study conducted on U266 MM cell line revealed an IC50value of 9.8±0.7μM. CLF also showed a synergistic inhibition effect in combination with cisplatin. In mechanistic assays, CLF treatment caused mitochondrial membrane depolarization, change in cell membrane asymmetry and increase in caspase-3 activity; indicating to an intrinsic apoptosis mechanism. This study provides new evidence for the anticancer effect of CLF on U266 cell line. Further in vivo and clinical studies are warranted to evaluate its therapeutic potential for MM treatment.
authors.affiliation: Middle East Technical University, Biotechnology Graduate Program, Üniversiteler Mahallesi Dumlupınar Bulvarı No:1, 06800 Çankaya Ankara, Turkey. Electronic address: ipekdurusu@gmail.com.
authors.forename: İpek Z
authors.initials: İZ
authors.lastname: Durusu
authors.affiliation: Middle East Technical University, Biochemistry Graduate Program, Üniversiteler Mahallesi, Dumlupınar Bulvarı No:1, 06800 Çankaya Ankara, Turkey. Electronic address: husnugil.hazal@gmail.com.
authors.forename: Hazal H
authors.initials: HH
authors.lastname: Hüsnügil
authors.affiliation: Middle East Technical University, Biotechnology Graduate Program, Üniversiteler Mahallesi Dumlupınar Bulvarı No:1, 06800 Çankaya Ankara, Turkey. Electronic address: hevalatas@gmail.com.
authors.forename: Heval
authors.initials: H
authors.lastname: Ataş
authors.affiliation: Middle East Technical University, Biotechnology Graduate Program, Üniversiteler Mahallesi Dumlupınar Bulvarı No:1, 06800 Çankaya Ankara, Turkey. Electronic address: aysenurbiber@gmail.com.
authors.forename: Ayşenur
authors.initials: A
authors.lastname: Biber
authors.affiliation: Middle East Technical University, Biochemistry Graduate Program, Üniversiteler Mahallesi, Dumlupınar Bulvarı No:1, 06800 Çankaya Ankara, Turkey. Electronic address: selin_gerekci@hotmail.com.
authors.forename: Selin
authors.initials: S
authors.lastname: Gerekçi
authors.affiliation: Middle East Technical University, Biochemistry Graduate Program, Üniversiteler Mahallesi, Dumlupınar Bulvarı No:1, 06800 Çankaya Ankara, Turkey. Electronic address: ezgi.gulec@metu.edu.tr.
authors.forename: Ezgi A
authors.initials: EA
authors.lastname: Güleç
authors.affiliation: Middle East Technical University, Biotechnology Department and Center of Excellence in Biomaterials and Tissue Engineering and Central Laboratory, Üniversiteler Mahallesi, Dumlupınar Bulvarı No:1, 06800 Çankaya Ankara, Turkey. Electronic address: dr.can.ozen@gmail.com.
authors.forename: Can
authors.initials: C
authors.lastname: Özen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use; D002991:Clofazimine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004357:Drug Synergism; D006801:Humans; D020128:Inhibitory Concentration 50; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D002991:Clofazimine; D002945:Cisplatin
keywords: Apoptosis; Cancer; Clofazimine; Multiple myeloma; Synergism