Anticancer effect and combination potential of clofazimine in multiple myeloma

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2016

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Durusu, İpek Zeynep

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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 viability of a panel of hematological cell lines (Jurkat, U266, Namalwa, K562, HL60) treated with CLF is screened. Dose and time response effect of CLF on U266 cell line is evaluated and anti-cancer effect of CLF combination treatment is examined using CellTiter Blue assay. For apoptosis JC-1, Caspase 3 and PE Annexin V-7 AAD assays are performed. CLF (10 μM, 24 h) showed growth suppression on all cell lines, highest on U266 (72%). It has an IC50 value of 9.87 ± 0.9 μM and has synergistic effect in combination with cisplatin. Cell cycle analysis indicates accumulation of cell population at S phase. CLF has apoptotic effect on U266 cells as, mitochondrial membrane depolarized cells 44, 67.8, 80.2 percent increased, caspase 3 positive cells 19.1, 41.3, 43,2 percent increased and early apoptotic cells 18.9, 39.3, 62,9 percent increased compared to control group at 12, 24 and 48 h respectively. Clofazimine has potent anticancer effect on U266 MM cell line. Clofazimine in vivo studies, alone and in combination with cisplatin, are warranted to evaluate its therapeutic potential for MM treatment.

Subject Keywords

Apoptosis., Cell lines., Clofazimine., Multiple myeloma., Cancer, Hematopoietic system

URI

http://etd.lib.metu.edu.tr/upload/12619878/index.pdf
https://hdl.handle.net/11511/25553

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Graduate School of Natural and Applied Sciences, Thesis

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Citation Formats

İ. Z. Durusu, “Anticancer effect and combination potential of clofazimine in multiple myeloma,” Ph.D. - Doctoral Program, Middle East Technical University, 2016.