title: Antiproliferative Activity of a New Nitrosyl Iron Complex with Cysteamine in Human Tumor Cells In Vitro.
abstract: We studied cytotoxic activity of a new NO-releasing tetranitrosyl binuclear iron complex with cysteamine (CysAm) for human tumor cells, the relationship between the expression of O6-methylguanine-DNA methyltransferase (MGMT) and cell sensitivity to CysAm, and apoptosis-inducing capacity of this preparation. It was found that histogenetically different cell lines are characterized by different sensitivity to CysAm, and this parameter correlated with the basal level of MGMT. CysAm induced apoptosis via activation of caspases 3 and 7. These data suggest that CysAm can be considered as a potential antitumor agent, but definitive conclusions can be made after preclinical trials.
authors.affiliation: Laboratory of Cell Immunity, Laboratory of Experimental Cheotherapy, N. N. Blokhin Cancer Research Center, Russian Ministry of Health, Moscow, Russia. msvz@yandex.ru.
authors.forename: O S
authors.initials: OS
authors.lastname: Zhukova
authors.affiliation: Laboratory of Cell Immunity, Laboratory of Experimental Cheotherapy, N. N. Blokhin Cancer Research Center, Russian Ministry of Health, Moscow, Russia.
authors.forename: Z S
authors.initials: ZS
authors.lastname: Smirnova
authors.affiliation: Laboratory of Cell Immunity, Laboratory of Experimental Cheotherapy, N. N. Blokhin Cancer Research Center, Russian Ministry of Health, Moscow, Russia.
authors.forename: I O
authors.initials: IO
authors.lastname: Chikileva
authors.affiliation: Laboratory of Cell Immunity, Laboratory of Experimental Cheotherapy, N. N. Blokhin Cancer Research Center, Russian Ministry of Health, Moscow, Russia.
authors.forename: M V
authors.initials: MV
authors.lastname: Kiselevskii
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000494:pharmacology*; D003543:Cysteamine / Q000737:chemistry*; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects; D045643:DNA Repair Enzymes / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D006801:Humans; D007501:Iron / Q000737:chemistry*; D020014:K562 Cells; D009589:Nitrogen Oxides / Q000737:chemistry*; D009928:Organ Specificity; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D009589:Nitrogen Oxides; D025521:Tumor Suppressor Proteins; D003543:Cysteamine; C073661:dinitrosyl iron complex; D007501:Iron; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes
keywords: NO-generating nitosyl iron complex; O6-methylguanine-DNA methyltransferase (MGMT); apoptosis; cytotoxic activity; human tumor cells