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Title of article :
Clofilium, a potassium channel blocker, induces apoptosis of human promyelocytic leukemia (HL-60) cells via Bcl-2-insensitive activation of caspase-3
Author/Authors :
Choi، نويسنده , , Buyoung and Kim، نويسنده , , Hak-Yup and Lee، نويسنده , , Ki-Ho and Cho، نويسنده , , Youl-Hee and Kong، نويسنده , , Gu، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 1999
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Abstract :
We have demonstrated that clofilium, a potassium channel blocker, induces apoptosis on human promyelocytic leukemia (HL-60) cells. Cells treated with clofilium led to suppression of viability and proliferation in both time and concentration-dependent manners. Nuclear DAPI staining and electronmicroscopic examination revealed typical nuclear features of apoptosis in cells treated with clofilium that was further verified in DNA fragmentation analysis. Flow cytometry analysis with FITC-annexin V and propidium iodide (PI) revealed that apoptotic cell population with Annexin V+/PI− increased gradually from <2% at 0 h, to 20% at 4 h and 29% at 16 h after exposure to 10 μM clofilium in HL-60 cells. Furthermore, fluorometric immunosorbent enzyme assay for activity of caspase-3 showed approximately a 10-fold increase of activity in cells treated with 10 μM of clofilium for 2–3 h compared with the basal level of its activity in untreated control cells. Immunoblotting analysis revealed proteolytic cleavage of caspase-3 and subsequent cleavage of PARP. However, there was no significant change of Bcl-2 and Bax proteins. These results indicate that clofilium exerts antiproliferative action and growth inhibition on HL-60 through induction of apoptosis which is mediated via Bcl-2-insensitive activation of caspase-3, and suggest chemotherapeutic and cytostatic potentials of this compound in human leukemias.
Keywords :
apoptosis , Clofilium , Potassium channel blocker , Cancer chemotherapy , Human promyelocytic leukemia (HL-60) cell
Journal title :
Cancer Letters
Journal title :
Cancer Letters
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