title: Mechanism of cell death induced by spermine and amine oxidase in mouse melanoma cells.
abstract: Polyamines such as spermine, spermidine and putrescine are necessary for cell proliferation and are detected at higher concentrations in most tumor tissues, compared to normal tissues. The amine oxidase enzymes can generate cytotoxic products such as hydrogen peroxide and aldehydes from these polyamines. This study investigates the mechanisms of cell death in B16-F0 mouse melanoma tumor cells exposed to bovine serum amine oxidase and exogenous spermine. The bovine serum amine oxidase/spermine enzymatic system induced inhibition of cell proliferation in B16-F0 melanoma cells and cell death by both apoptotic and necrotic processes. Bovine serum amine oxidase or spermine, alone, did not induce cytotoxicity or cell death by apoptosis, indicating that the enzymatic reaction products were responsible. Catalase and NAD-dependent aldehyde dehydrogenase, inhibitors of hydrogen peroxide and aldehydes, respectively, decreased cell death by apoptosis and necrosis. This further confirms that the cytotoxic products are responsible for causing cell death. Use of inhibitors of different caspases showed that melanoma cells were sensitive to processes involving caspase-3 and -9, but were insensitive to caspase-6. Bovine serum amine oxidase in the presence of spermine could be useful as a promising new tool for anticancer treatment by the selective generation of toxic compounds from polyamines in tumors.
authors: Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Québec, H3C 3P8, Canada. averill.diana@uqam.ca
authors: Diana A
authors: DA
authors: Averill-Bates
authors: Qixiang
authors: Q
authors: Ke
authors: André
authors: A
authors: Tanel
authors: Julie
authors: J
authors: Roy
authors: Guy
authors: G
authors: Fortier
authors: Enzo
authors: E
authors: Agostinelli
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000494:pharmacology; D006631:Amine Oxidase (Copper-Containing) / Q000494:pharmacology*; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002374:Catalase / Q000494:pharmacology; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D009336:Necrosis; D013096:Spermine / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D017304:Annexin A5; D013096:Spermine; D002374:Catalase; D000444:Aldehyde Dehydrogenase; D006631:Amine Oxidase (Copper-Containing)