RRC ID 52319
著者 Umemura M, Kim JH, Aoyama H, Hoshino Y, Fukumura H, Nakakaji R, Sato I, Ohtake M, Akimoto T, Narikawa M, Tanaka R, Fujita T, Yokoyama U, Taguri M, Okumura S, Sato M, Eguchi H, Ishikawa Y.
タイトル The iron chelating agent, deferoxamine detoxifies Fe(Salen)-induced cytotoxicity.
ジャーナル J Pharmacol Sci
Abstract Iron-salen, i.e., μ-oxo-N,N'-bis(salicylidene)ethylenediamine iron (Fe(Salen)) was a recently identified as a new anti-cancer compound with intrinsic magnetic properties. Chelation therapy has been widely used in management of metallic poisoning, because an administration of agents that bind metals can prevent potential lethal effects of particular metal. In this study, we confirmed the therapeutic effect of deferoxamine mesylate (DFO) chelation against Fe(Salen) as part of the chelator antidote efficacy. DFO administration resulted in reduced cytotoxicity and ROS generation by Fe(Salen) in cancer cells. DFO (25 mg/kg) reduced the onset of Fe(Salen) (25 mg/kg)-induced acute liver and renal dysfunction. DFO (300 mg/kg) improves survival rate after systematic injection of a fatal dose of Fe(Salen) (200 mg/kg) in mice. DFO enables the use of higher Fe(Salen) doses to treat progressive states of cancer, and it also appears to decrease the acute side effects of Fe(Salen). This makes DFO a potential antidote candidate for Fe(Salen)-based cancer treatments, and this novel strategy could be widely used in minimally-invasive clinical settings.
巻・号 134(4)
ページ 203-210
公開日 2017-8-1
DOI 10.1016/j.jphs.2017.07.002
PII S1347-8613(17)30101-9
PMID 28779994
MeSH Acute Kidney Injury / chemically induced Animals Antidotes* Antineoplastic Agents / administration & dosage Antineoplastic Agents / adverse effects* Antineoplastic Agents / toxicity* Chelating Agents / administration & dosage Chelating Agents / adverse effects* Chelating Agents / toxicity* Chemical and Drug Induced Liver Injury / etiology Deferoxamine / pharmacology* Deferoxamine / therapeutic use* Dose-Response Relationship, Drug Ethylenediamines / administration & dosage Ethylenediamines / adverse effects* Ethylenediamines / toxicity* Humans Iron / administration & dosage Iron / adverse effects* Iron / toxicity* Iron Chelating Agents / pharmacology* Iron Chelating Agents / therapeutic use* Rabbits Reactive Oxygen Species / metabolism Tumor Cells, Cultured
IF 2.575
引用数 16
リソース情報
ヒト・動物細胞 OVK18(RCB1903)