Anti-cancer effect of clofazimine as a single agent and in combination with cisplatin on U266 multiple myeloma cell line

Durusu I. Z., Husnugil H. H., ATAŞ H., BİBER A., GEREKCİ S., Gulec E. A., ...Daha Fazla

Leukemia Research, cilt.55, ss.33-40, 2017 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 55
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1016/j.leukres.2017.01.019
  • Dergi Adı: Leukemia Research
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.33-40
  • Anahtar Kelimeler: Cancer, Multiple myeloma, Clofazimine, Apoptosis, Synergism, MITOCHONDRIAL POTASSIUM CHANNEL, HEPATOCELLULAR-CARCINOMA, THERAPEUTIC TARGETS, INDUCED APOPTOSIS, ION CHANNELS, CANCER-CELLS, PHASE-II, IN-VITRO, KV1.3, TRANSPLANTATION
  • Orta Doğu Teknik Üniversitesi Adresli: Evet

Özet

© 2017 Elsevier LtdMultiple 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 (10 μM, 24 h) 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 IC50 value of 9.8 ± 0.7 μM. 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.