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 (MbetaCD) 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 ([Ca(2+)](i)) in MOLT-4 cells, and 2CdA-induced apoptosis was partly inhibited by the Ca(2+) chelators BAPTA-AM and EGTA, and the L-type Ca(2+) 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 Ca(2+) influx via the plasma membrane.
Takahashi
Eriko
E
Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18 jo Nishi 9 chome, Sapporo, Japan.
Inanami
Osamu
O
Ohta
Toshio
T
Matsuda
Akira
A
Kuwabara
Mikinori
M
D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000494:pharmacology; D017338:Cladribine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005372:Filipin / Q000494:pharmacology; D006801:Humans; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism*; D013997:Time Factors; D047392:beta-Cyclodextrins / Q000494:pharmacology
D002614:Chelating Agents; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D017338:Cladribine; D004533:Egtazic Acid; D005372:Filipin; D009543:Nifedipine; D002118:Calcium