Apoptosis in neuroblastomas induced by interferon-gamma involves the CD95/CD95L pathway.
METHODS
The CD95/CD95 ligand (CD95L) system is a key regulator of apoptosis. To evaluate a possible role of the CD95/CD95L system in human neuroblastoma (NB) cells, we investigated the constitutive and interferongamma (INFgamma)-induced expression of CD95 and CD95L, and CD95-mediated cell death in the SK-N-BE(2) cell line.


RESULTS
Modulation of CD95/CD95L expression and triggering of an autocrine apoptotic mechanism by IFNgamma suggest a potential role for INFgamma as a therapeutic agent for NB.


CONCLUSIONS
The evidence that retinoids induce apoptosis via tissue transglutaminase (tTG) and that N-methyl-D-aspartate (NMDA) and gp120 act through the nitric oxide synthase (NOS) activation pathway, indicates the existence of different molecular mechanisms of action, whose pharmacological exploitation might be used in an additive fashion.
Annicchiarico-Petruzzelli
M
M
IDI-IRCCS, Biochemistry Lab, University of Rome Tor Vergata, Italy.
Bernassola
F
F
Lovat
P E
PE
Redfern
C P
CP
Pearson
A D
AD
Melino
G
G
D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D053222:Fas Ligand Protein; D019204:GTP-Binding Proteins / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D015699:HIV Envelope Protein gp120 / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D017136:Ion Transport; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D016202:N-Methylaspartate / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000502:physiology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D011503:Transglutaminases / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019014:fas Receptor / Q000235:genetics / Q000502:physiology*
D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D015699:HIV Envelope Protein gp120; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D019014:fas Receptor; D009569:Nitric Oxide; D016202:N-Methylaspartate; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D002118:Calcium