TTT, a novel free radical spin trap, induces apoptosis in sarcoma Yoshida cells in vivo: comparative investigations of its cytotoxicity in vitro.
In light of our previous SAR studies on nitroxides acting as less toxic anticancer agents, antioxidants and radioprotectors, we designed and tested, in vivo an in vitro, a new triradical spin trap -N,N',N"-tris-(l-oxyl-2,2,6,6-tetramethylpiperidine-4-yl)-1,3, 5-tnazine-2,4,6-triamine (TTT). The ability of TTT to act as an antitumor agent in vivo was investigated in pharmacological tests. The administration of TTT to rats bearing 3 day-old Sarcoma Yoshida (promotion phase of the disease) led to induction of apoptotic cell(s) death. Our results clearly indicated the suggested involvement of the free radical moiety of piperidine ring(s), thus indicating that the anticancer activity of nitroxide(s) may involve its intracellular redox reactions. To assess the relationship between the apoptotic effects of TTT in vivo and its possible cytotoxicity, we determined the relative antiproliferative and cytostatic potential of TTT in vitro as compared with this of the anticancer drugs: doxorubicin, aclarubicin and mitoxantrone, currently used in clinical practice in Poland. We found that TTT inhibits the growth and proliferation of two immortalized cell types-hamster B14 cell line and mouse NIH 3T3 fibroblasts which we used as a model for neoplastic phenotype, in a dose-dependent manner.
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Institute of Applied Radiation Chemistry, Technical University of Lódź, Poland. media@mitr.p.lodz.pl
Kochman
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Skolimowski
J
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Koceva-Chyła
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D016475:3T3 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001391:Azo Compounds / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D006224:Cricetinae; D051379:Mice; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D012517:Sarcoma, Yoshida / Q000473:pathology*; D013113:Spin Labels
D000970:Antineoplastic Agents; D001391:Azo Compounds; C403748:N,N',N''-tris-(1-oxyl-2,2,6,6-tetramethylpiperidine-4-yl)-1,3,5-tnazine-2,4,6-triamine; D010880:Piperidines; D013113:Spin Labels