Induction of Apoptosis by Intracellular Ca2+ Inhibitors in Human Leukemic HL-60 Cells
이용수, 백진현, 김정애, 손한철, 권경술, 김규원,
소속 상세정보
이용수 ( Lee Yong-Soo )
관동대학교 의과대학 생리학교실
백진현 ( Baek Jin-Hyen )
부산대학교 분자생물학과
김정애 ( Kim Jung-Ae )
영남대학교 약학대학
손한철 ( Son Han-Chul )
부산대학교 의과대학 암연구소
권경술 ( Kwon Kyung-Sool )
부산대학교 의과대학 암연구소
김규원 ( Kim Kyu-Won )
부산대학교 분자생물학과
KMID : 0603519980030010058
Abstract
Apoptosis which plays an important role in tumorigenesis as well as embryo development has been known to be induced by the sustained rise in intracellular free Ca2+. However, many studies have shown that apoptosis is not always related with increased intracellular free calcium concentration. In the present study, the effect of several intracellular Ca2+ inhibitors on cell death was investigated in order to evaluate the role of intracellular Ca2+ signal inhibition in apoptotic cell death using HL-60 human promyelocytic leukemia cells as a model cellular system. Plasma membrane Ca2+ channel blockers (verapamil, nifedipine and diltiazem), intracellular Ca2+ release blockers (dantrolene, TMB-8 and ruthenium red), an extracellular Ca2+ chelator (EGTA) and an intracellular Ca2+ chelator (BAPT/UAM) were used as intracellular Ca2+ inhibitors in the experiments. Treatment with these agents resulted in a concentration-dependent decreased cell viability assessed by MTT assay. These agents also induced genomic DNA fragmentation, a hallmark of apoptosis, indicating that the mechanism by which these agents induce cell death was through apoptosis. No effect of cycloheximide, a protein synthesis inhibitor, on the cell death was observed, implying that new protein synthesis may not be required for the apoptosis caused by these intracellular Ca2+ inhibitors. These results suggest that the inhibition of intracellular Ca2+ signals may be involved in the induction of apoptosis in HL-60 cells.
키워드
HL-60 cell; Apoptosis; Cycloheximide; BATA/AM; Dantrolene; Diltiazem@EGTA; Nifedipine; Ruthenium red; Verapamil
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