Lipid raft disruption prevents apoptosis induced by 2-chloro-2′-deoxyadenosine (Cladribine) in leukemia cell lines

To clarify the role of lipid rafts in 2-chloro-2'-deoxyadenosine (2CdA; Cladribine)-induced apoptosis, the effects of disruption of lipid rafts by methyl-beta-cyclodextrin (M beta CD) and filipin on 2CdA-induced apoptosis were investigated in four human acute lymphoblastic leukemia (ALL) cell lines comprised of T cells (MOLT-4, Jurkat) and B cells (NALM, BALL-1). The disruption of lipid rafts significantly inhibited 2CdA-induced apoptosis, indicating the crucial role of lipid rafts in the induction of apoptosis in leukemia cells. These reagents significantly inhibited 2CdA-induced elevation of the intracellular calcium concentration ([Ca2+](i)) in MOLT-4 cells, and 2CdA-induced apoptosis was partly inhibited by the Ca2+ chelators BAPTA-AM and EGTA, and the L-type Ca2+ channel blocker nifedipine. On the other hand, they had no effects on the cellular uptake of 2CdA. These results indicated that lipid rafts partly contributed to 2CdA-induced apoptosis by regulating Ca2+ influx via the plasma membrane. (c) 2006 Elsevier Ltd. All rights reserved.