Polyamine biosynthesis as a target to inhibit apoptosis of non-tumoral cells.
Growing evidence suggests a role for polyamines in apoptosis, although the relationship appears to be complex. alpha-Difluoromethylornithine (DFMO), a largely used ornithine decarboxylase inhibitor, is cytostatic, hardly cytotoxic and may even increase the resistance of tumour cells to some apoptotic stimuli. This may represent a problem in cancer therapy, where the killing of tumoral cells would be a desired effect, but could be an advantage in other pathological contexts related to an excess of apoptosis, such as cardiovascular diseases, stem cell transplantation, arthritis and infections. In different cellular models, polyamine depletion following treatment with polyamine biosynthesis inhibitors appears to inhibit mitochondrial and death receptor pathways of apoptosis by affecting key proteins. These studies indicate that inhibition of polyamine biosynthesis may prevent or reduce the apoptotic response triggered by a variety of stimuli in non-tumoral cells, such as cardiac cells, stem cells, chondrocytes, macrophages and intestinal epithelial cells.
Flamigni
F
F
Department of Biochemistry "G. Moruzzi", University of Bologna, Bologna, Italy. flavio.flamigni@unibo.it
Stanic'
I
I
Facchini
A
A
Cetrullo
S
S
Tantini
B
B
Borzì
R M
RM
Guarnieri
C
C
Caldarera
C M
CM
D000578:Amidines / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015317:Biogenic Polyamines / Q000096:biosynthesis*; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D000518:Eflornithine / Q000494:pharmacology; D006801:Humans; D007189:Indans / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D065108:Ornithine Decarboxylase Inhibitors; D010447:Peptide Hydrolases / Q000378:metabolism; D011700:Putrescine / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013095:Spermidine / Q000378:metabolism
D000578:Amidines; D015317:Biogenic Polyamines; D007189:Indans; D065108:Ornithine Decarboxylase Inhibitors; C082408:4-amidinoindan-1-one 2'-amidinohydrazone; D010447:Peptide Hydrolases; D020169:Caspases; C108711:DEVDase; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine