| Literature DB >> 28779994 |
Masanari Umemura1, Jeong-Hwan Kim2, Haruki Aoyama3, Yujiro Hoshino4, Hidenobu Fukumura5, Rina Nakakaji6, Itaru Sato7, Makoto Ohtake8, Taisuke Akimoto9, Masatoshi Narikawa10, Ryo Tanaka11, Takayuki Fujita12, Utako Yokoyama13, Masataka Taguri14, Satoshi Okumura15, Motohiko Sato16, Haruki Eguchi17, Yoshihiro Ishikawa18.
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.Entities:
Keywords: Anti-cancer; Antidote; Chelate; Deferoxamine (DFO); Fe(Salen)
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Year: 2017 PMID： 28779994 DOI： 10.1016/j.jphs.2017.07.002
Source DB: PubMed Journal: J Pharmacol Sci ISSN： 1347-8613 Impact factor: 3.337