Glucocorticoid-induced lymphoma cell death: the good and the evil.
Glucocorticoid hormones and their synthetic derivatives are widely used in therapy due to their strong anti-inflammatory and immunosuppressive potential. While the molecular basis of the anti-inflammatory action is to date at least partially understood, knowledge regarding the mechanism underlying glucocorticoid effects on the immune system is rather fragmentary. The immunosuppression could be attributed to at least two distinct processes: inhibition of the production of growth mediators and glucocorticoid-induced cell death. The mechanism of glucocorticoid-induced cell death can be divided into two steps, a reversible growth inhibition and cell lysis. The first step is characterized by many metabolic alterations typical of the catabolic potential of corticosteroids. After a delay of several hours activation of an endonuclease appears to initiate the lytic phase. By the action of this endonuclease the DNA is fragmented. In opposition to the chromatin damage, poly(ADP-ribosyl)ation is activated in order to stabilize the chromatin structure until the antagonistic potential is exhausted and the cells die. Therefore it can be speculated that the lethal event in glucocorticoid-induced cell death is a destruction of the regular chromatin structure.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002843:Chromatin / Q000187:drug effects / Q000648:ultrastructure; D004273:DNA, Neoplasm / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008223:Lymphoma / Q000473:pathology*; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D002843:Chromatin; D004273:DNA, Neoplasm; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D009363:Neoplasm Proteins; D011065:Poly(ADP-ribose) Polymerases; D004706:Endodeoxyribonucleases