2-deoxy-d-ribose-induced apoptosis in HL-60 cells is associated with the cell cycle progression by spermidine.
The presence of polyamines is required for the apoptotic program triggered by 2-deoxy-D-ribose (dRib) in HL-60 cells, but their oxidative metabolites does not appear to be involved in the oxidative stress caused by the sugar. The present study points to a relationship between spermidine-induced G1 to S phase transition and the onset of dRib-induced apoptosis. Conversely, the G1 block induced by alpha-difluoromethylornithine (DFMO) is associated with a protective effect against dRib-induced cell suicide. Replenishment of the intracellular spermidine pool by exogenous putrescine and spermidine induces cell cycle progression and restores apoptotic levels. The present data indicate that the induction of cell cycle progression by spermidine is a condition facilitating the activation of the apoptotic process by dRib.
Giuseppina Monti
M
M
Department of Biomedical Sciences, University of Modena, Modena, Italy. mgmonti@mail.unimo.it
Ghiaroni
S
S
Barbieri
D
D
Franceschi
C
C
Marverti
G
G
Moruzzi
M S
MS
D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D003855:Deoxyribose / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000518:Eflornithine / Q000494:pharmacology; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009861:Onium Compounds / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000378:metabolism; D065108:Ornithine Decarboxylase Inhibitors; D018384:Oxidative Stress / Q000187:drug effects; D011700:Putrescine / Q000494:pharmacology; D013095:Spermidine / Q000378:metabolism / Q000494:pharmacology*; D013096:Spermine / Q000031:analogs & derivatives / Q000494:pharmacology
D000975:Antioxidants; D009861:Onium Compounds; D009943:Organophosphorus Compounds; D065108:Ornithine Decarboxylase Inhibitors; C059685:N(1),N(11)-diethylnorspermine; D013096:Spermine; D003855:Deoxyribose; D013095:Spermidine; C013289:tetraphenylphosphonium; D011700:Putrescine; D000111:Acetylcysteine; D000518:Eflornithine