Induction of calcium influx from extracellular fluid by beauvericin in human leukemia cells

Abstract

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 Ca 2+ concentration ([Ca 2+] i) may play an important role in beauvericin-induced cell death in CCRF-CEM cells. In this study, the effect of beauvericin on [Ca 2+] i and the possible mechanism responsible for the changes of [Ca 2+] i in CCRF-CEM cells were investigated. Beauvericin caused a rapid and sustained [Ca 2+] i rise in a dose-dependent manner. Excess extracellular Ca 2+ facilitated beauvericin-induced [Ca 2+] i rise by adding 1 mM CaCl 2 in the bathing medium. On the other hand, beauvericin-induced [Ca 2+] i rise was prevented in Ca 2+-free Tyrode’s solution by 200 μM EGTA. In addition, beauvericin-induced [Ca 2+] i rise was also attenuated by intracellular Ca 2+ chelator-BAPTA/AM. It is worthy to note that neither the voltage-dependent Ca 2+ channel blocker, nimodipine, nor depletion of intracellular Ca 2+ with thapsigargin, an endoplasmic reticulum Ca 2+ pump inhibitor, has any effect on beauvericin-induced [Ca 2+] i rise. The data from present study indicate that beauvericin acts as a potent Ca 2+mobilizer by stimulating extracellular Ca 2+ influx CCRF-CEM cells.