Cytotoxıc effect of KV1.3 potassium channel blocker clofazimine on hematological cancer cell lines

Ipek, Durusu
Husnugil, Hazal
Heval, Ates
Özen, Can
Introduction / Aim: Potassium ion channels play an important role in regulating cell proliferation by maintenance of the membrane potential and subsequent Ca2+ signaling. Out of 80 known human K-channel genes, only the voltage-gated K-channel Kv1.3 and the calcium-gated K-channel KCa3.1 are expressed in lymphocytes, with expression levels varying greatly depending on maturation and activation status. As indicated by previous studies, Kv1.3 is involved in the pathogenesis of various hematological malignancies. Aim of this study was a) to compare the expression levels of Kv1.3 in various hematological cancer cell lines and b) to determine the cytotoxic effect of a specific Kv1.3 blocker, clofazimine, on Kv1.3-positive and negative cells. Materials and Methods: HL60 (acute promyelocytic leukemia), Namalwa and Ramos (Burkitt lymphoma), K562 (chronic myelogenous leukemia), Jurkat (T cell leukemia), Cem (Acute lymphoblastic leukemia) and U266 (multiple myeloma) cell lines were used in this study. Expression level of the Kv1.3 was determined using qRTPCR. Potassium ion flux was measured using a thalliumsensitive fluorescence-based assay (FluxOR, Invitrogen). Cell viability assesment was performed with Alamar blue assay. Results: Hematological cancer cell lines showed variable Kv1.3 expression levels as determined by qRT-PCR. Cem had the highest expression whereas HL-60 and K562 showed no significant channel expression. Specific Kv1.3 blocker clofazimine inhibited potassium ion flux in Cem and Jurkat cells. As expected, there was no blocking effect on Kv1.3-negative cell line K562. We also observed a dose-dependent cytotoxic effect on both Cem and Jurkat cells but not on K562. Conclusion: Potassium ion channel Kv1.3 is highly expressed in majority of the tested hematological cancer cell lines. Specific Kv1.3 blocker clofazimine showed cytotoxic effect on Kv1.3-positive cell lines but not on Kv1.3- negative cell line K562. Collectively, these results suggest that clofazimine exerts its cytotoxic effect mainly through Kv1.3 channel.


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Citation Formats
D. Ipek, H. Husnugil, A. Heval, and C. Özen, “Cytotoxıc effect of KV1.3 potassium channel blocker clofazimine on hematological cancer cell lines,” İstanbul, Turkey, 2015, p. 202, Accessed: 00, 2021. [Online]. Available: