L-carnitine inhibits apoptotic DNA fragmentation induced by a new spin-labeled derivative of podophyllotoxin via caspase-3 in Raji cells.
L-carnitine (beta-hydroxy-trimethylaminobutyric acid) plays an essential metabolic role that consists of transferring the long chain fatty acids through the mitochondrial barrier, thus allowing their energy-yielding oxidation. GP7 (4-[4''-(2'', 2'', 6'', 6''-tetramethyl-l''-piperidinyloxy) amino] -4'-demethyl-epipodophyllotoxin) is a new spin-labeled derivative of podophyllotoxin semi-synthesized by our university. In this study, we examined the activity of L-carnitine in GP7-induced apoptosis in Burkitt's lymphoma cell line, Raji. GP7 induced time- and dose-dependent apoptotic DNA fragmentation accompanied by caspase-3 activation in Raji cells, and the kinetics of caspase-3 activation induced by GP7 was well correlated with that of apoptotic DNA fragmentation. L-carnitine treatment prevented GP7-induced caspase-3 activation, suppressed caspase-3 cleavage and abrogated GP7-induced apoptotic DNA fragmentation in Raji cells. Our findings suggest that L-carnitine is a potent anti-apoptotic agent to human lymphoma cells and may exert its anti-apoptotic effect via inhibition of caspase-3 activity in GP7-treated Raji cells.
Qi
She-Ning
SN
Department of Histology and Embryology, School of Basic Medicine, Lanzhou University, PR China. qishening@hotmail.com
Zhang
Zhi-Feng
ZF
Wang
Zhen-Yun
ZY
Yoshida
Akira
A
Ueda
Takanori
T
D017209:Apoptosis / Q000187:drug effects; D002051:Burkitt Lymphoma / Q000201:enzymology*; D002331:Carnitine / Q000494:pharmacology*; D053148:Caspase 3; D061945:Caspase Inhibitors; D045744:Cell Line, Tumor; D004247:DNA / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology
D061945:Caspase Inhibitors; C071346:GP 7; D004247:DNA; C505407:CASP3 protein, human; D053148:Caspase 3; D011034:Podophyllotoxin; D002331:Carnitine