Anti-Cancer Effects of Clofazimine As a Single Agent and in Combination with Cisplatin in Multiple Myeloma

Date

2016-12-02

Author

Durusu, Ipek
Hüsnügil, Hepşen Hazal
Atas, Heval
Biber, Aysenur
Gerekci, Selin
Gulec, Aliye Ezgi
Özen, Can

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

152
views

0
downloads

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 IC50 value 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.

Subject Keywords

Hematology

URI

https://hdl.handle.net/11511/54997

Collections

Department of Biology, Conference / Seminar

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...
The low frequency of defective TPMT alleles in Turkish population: A study on pediatric patients with acute lymphoblastic leukemia Tumer, Tugba Boyunegmez; Ulusoy, Gulen; Adalı, Orhan; Sahin, Gurses; Gozdasoglu, Sevgi; Arinc, Ennel (Wiley, 2007-10-01) 6-Mercaptopurine (6MP) is an essential anticancer drug used in the treatment of childhood acute lymphoblastic leukemia (ALL). Thiopurine methyltransferase (TPMT) polymorphisms are the major determinants of interindividual differences in the severe toxicity or efficacy of 6MP Four variant alleles, TPMT*2, TPMT*3A, TPMT*3B, and TPMT*3C, are responsible over the 80% of low or undetectable enzyme activity. The frequencies of these variants were investigated among 106 children with ALL in Turkish population. TPM...
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...
Repurposing of antipsychotic agent trifluoperazine for multiple myeloma treatment: in vitro studies Ataş, Heval; Özen, Can; Erdoğ, Aslı; Department of Biotechnology (2016) 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...
An update on molecular biology and drug resistance mechanisms of multiple myeloma Mutlu, Pelin; Gündüz, Ufuk (Elsevier BV, 2015-12) Multiple myeloma (MM), a neoplasm of plasma cells, is the second most common hematological malignancy. Incidance rates increase after age 40. MM is most commonly seen in men and African-American population. There are several factors to this, such as obesity, environmental factors, family history, genetic factors and monoclonal gammopathies of undetermined significance (MGUS) that have been implicated as potentially etiologic. Development of MM involves a series of complex molecular events, including chromos...

Citation Formats

I. Durusu et al., “Anti-Cancer Effects of Clofazimine As a Single Agent and in Combination with Cisplatin in Multiple Myeloma,” 2016, vol. 128, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/54997.