L-carnitine inhibits apoptotic DNA fragmentation induced by a new spin-labeled derivative of podophyllotoxin via caspase-3 in Raji cells

Oncol Rep. 2006 Jan;15(1):119-22.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Burkitt Lymphoma / enzymology*
  • Carnitine / pharmacology*
  • Caspase 3
  • Caspase Inhibitors*
  • Cell Line, Tumor
  • DNA / drug effects
  • DNA Fragmentation / drug effects*
  • Enzyme Activation / drug effects
  • Humans
  • Podophyllotoxin / analogs & derivatives*
  • Podophyllotoxin / antagonists & inhibitors
  • Podophyllotoxin / pharmacology

Substances

  • Caspase Inhibitors
  • GP 7
  • DNA
  • CASP3 protein, human
  • Caspase 3
  • Podophyllotoxin
  • Carnitine