Induction of calcium influx from extracellular fluid by beauvericin in human leukemia cells.
Beauvericin, a cyclic hexadepsipeptide, is a mycotoxin that can induce cell death in human lymphoblastic leukemia CCRF-CEM cells. Our previous data have shown that beauvericin induces cell death in CCRF-CEM cells in a dose- and time-dependent manner, and that this beauvericin-induced cell death can be prevented by administration of intracellular calcium chelator-BAPTA. Therefore, the intracellular Ca2+ concentration ([Ca2+]i) may play an important role in beauvericin-induced cell death in CCRF-CEM cells. In this study, the effect of beauvericin on [Ca2+]i and the possible mechanism responsible for the changes of [Ca2+]i in CCRF-CEM cells were investigated. Beauvericin caused a rapid and sustained [Ca2+]i rise in a dose-dependent manner. Excess extracellular Ca2+ facilitated beauvericin-induced [Ca2+]i rise by adding 1 mM CaCl2 in the bathing medium. On the other hand, beauvericin-induced [Ca2+]i rise was prevented in Ca2+-free Tyrode's solution by 200 microM EGTA. In addition, beauvericin-induced [Ca2+]i rise was also attenuated by intracellular Ca2+ chelator-BAPTA/AM. It is worthy to note that neither the voltage-dependent Ca2+ channel blocker, nimodipine, nor depletion of intracellular Ca2+ with thapsigargin, an endoplasmic reticulum Ca2+ pump inhibitor, has any effect on beauvericin-induced [Ca2+]i rise. The data from present study indicate that beauvericin acts as a potent Ca2+ mobilizer by stimulating extracellular Ca2+ influx CCRF-CEM cells.
Chen
Bing-Fang
BF
School of Medicine, Fu Jen Catholic University, 510 Chung-Cheng Rd., Hsin-Chuang, Taipei, Hsien 24205, Taiwan.
Tsai
Meng-Chao
MC
Jow
Guey-Mei
GM
D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D047630:Depsipeptides / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000378:metabolism*; D006801:Humans; D007945:Leukemia, Lymphoid / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D047630:Depsipeptides; C004456:beauvericin; D002118:Calcium