The iron chelating agent, deferoxamine detoxifies Fe(Salen)-induced cytotoxicity

Umemura, Masanari; Kim, Jeong Hwan; Aoyama, Haruki; Hoshino, Yujiro; Fukumura, Hidenobu; Nakakaji, Rina; Sato, Itaru; Ohtake, Makoto; Akimoto, Taisuke; Narikawa, Masatoshi; Tanaka, Ryo; Fujita, Takayuki; Yokoyama, Utako; Taguri, Masataka; Okumura, Satoshi; Sato, Motohiko; Eguchi, Hisashi; Ishikawa, Yoshihiro

doi:10.1016/j.jphs.2017.07.002

Cited by 49 publications

(39 citation statements)

References 26 publications

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“…We previously reported that Fe(Salen) nanoparticles (NP) showed potent, dose-dependent antitumor effects for 24 hours in various cancer cell lines 4 and increased generation of ROS in VX2, rabbit squamous cell carcinoma. 6,7 To evaluate the antitumor effect of Fe(Salen) in the rabbit model, we first evaluated the continuous antitumor effect of Fe(Salen) in VX2 cell lines for 2 days. The result showed that Fe(Salen) significantly inhibited cell proliferation of VX2 cells in a dose-dependent method for 2 days ( Figure 1A).…”

Section: Fe(salen) Showed Potent Antitumor Effect In Rabbit Squamoumentioning

confidence: 99%

“…By computer analysis, we previously searched a magnetic compound in a library with more than 3 million compounds. We recently identified an iron‐salen; that is, μ‐oxo‐ N , N ′‐ bis(salicylidene)ethylenediamine iron [Fe(Salen)] as a new antitumor organic compound with intrinsic magnetic property . The magnetic property of Fe(Salen) enables controlled drug delivery using a permanent or electric magnet.…”

Section: Introductionmentioning

confidence: 99%

“…The antitumor effect is similar to that of cisplatin. Fe(Salen) shows potent cytotoxicity, presumably through production of reactive oxygen species (ROS) that nicks DNA and then causes DNA damage . However, the mechanism of Fe(Salen) needs further investigation.…”

Section: Introductionmentioning

confidence: 99%

“…Based on these results, Fe(Salen) would be a potent, single‐drug anticancer agent in future clinical applications. Moreover, we have recently reported the therapeutic effect of deferoxamine mesylate (DFO) chelation against Fe(Salen) as part of chelator antidote efficacy . Giving DFO reduced cytotoxicity and ROS generation by Fe(Salen) in cancer cells and improved survival rate after systematic injection of a fatal dose of Fe(Salen) in mice.…”

Section: Introductionmentioning

confidence: 99%

“…We recently identified an iron-salen; that is, μ-oxo-N,N′-bis(salicylidene) ethylenediamine iron [Fe(Salen)] as a new antitumor organic compound with intrinsic magnetic property. [4][5][6][7][8] The magnetic property of Fe(Salen) enables controlled drug delivery using a permanent or electric magnet. The antitumor effect is similar to that of cisplatin.…”

Section: Introductionmentioning

confidence: 99%

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Simultaneous hyperthermia‐chemotherapy effect by arterial injection of Fe(Salen) for femur tumor

Umemura

Islam

Fukumura³

et al. 2018

Cancer Science

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We previously identified a novel nanomagnetic particle, N,N′‐bis(salicylidene)ethylenediamine iron [Fe(Salen)]. Fe(Salen) not only shows antitumor effects but also magnetic properties. We found that Fe(Salen) can be used for magnet‐guided drug delivery and visualization of accumulated drug by magnetic resonance imaging (MRI) because of its magnetism. In addition, Fe(Salen) can generate heat by itself when exposed to an alternating current magnetic field (AMF), resulting in a hyperthermia effect. Herein, we partly elucidated the antitumor mechanism of Fe(Salen) and carried out an i.v. repeated dose toxicity study to decide the therapeutic amount. Furthermore, we evaluated the antitumor effect of selective intra‐arterial injection or i.v. injection of Fe(Salen) by catheter and the hyperthermia effect of Fe(Salen) when exposed to AMF in vivo. We used a rabbit model grafted with VX2 cells (rabbit squamous cell carcinoma) on the right leg. Intra‐arterial injection of Fe(Salen) showed a greater antitumor effect than did i.v. injection. The combination of Fe(Salen) intra‐arterial injection and AMF exposure showed a greater antitumor effect than did either Fe(Salen) or methotrexate (MTX) without AMF exposure, suggesting that AMF exposure greatly enhanced the antitumor effect of Fe(Salen) by arterial injection by catheter. This is the first report that the effectiveness of Fe(Salen) was evaluated in the point of administration route; that is, selective intra‐arterial injection by catheter. Taken together, these results indicate a new administration route; that is, selective arterial injection of Fe(Salen) by catheter, and the development of a new strategy of simultaneous hyperthermia‐chemotherapy in the future.

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Section: Fe(salen) Showed Potent Antitumor Effect In Rabbit Squamoumentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Simultaneous hyperthermia‐chemotherapy effect by arterial injection of Fe(Salen) for femur tumor

Umemura

Islam

Fukumura³

et al. 2018

Cancer Science

Self Cite

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Synthesis, Characterization, Theoretical Studies, and Antimicrobial/Antitumor Potencies of Salen and Salen/Imidazole Complexes of Co (II), Ni (II), Cu (II), Cd (II), Al (III) and La (III)

Abdalla

Rahman

Abdelhamid

et al. 2020

Applied Organom Chemis

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Although salens and imidazoles are well-studied motifs among bioactive and therapeutic agents, their properties when combined in transition metal complexes are not well developed. To explore the structure/reactivity of this class of compounds, a salen-based ligand, namely (2,2 0-{1,2-ethanediylbis[nitrilo(E) methylylidene]}diphenol, S), and its binary (MS) and ternary (MSI) complexes (I = imidazole; M = Co (II), Ni (II), Cu (II), Cd (II), Al (III), and La (III)) have been synthesized and fully characterized by standard physicochemical and theoretical methods. Evidence from structural analysis tools along with DFT modeling revealed an unusual monobasic tridentate salen binding mode, involving the phenolic oxygen, the nitrogen of the azomethine group, and NH group formed via phenol-to-cyclohexadienone tautomerization, giving rise to a general molecular formula of MSI complexes as [M(S)(I) 2 (Cl)] for M (II) = Co, Ni, Cu and Cd or [M(S)(I)(Cl) 2 ] for M (III) = Al and La, respectively. The antimicrobial activities of S, MS, and MSI were screened against several bacterial and fungal strains. Of all tested complexes, CdS and CuSI were the most effective antimicrobials, giving larger inhibition zones than the reference antibiotics. The antimicrobial efficacy for the MS complexes follows the order: CdS > gentamicin > CuS > NiS > CoS > LaS > AlS > S, whereas MSI complex, potencies are ordered as CuSI > gentamicin > CdSI >NiSI > CoSI > LaSI > AlSI > S. In vitro cytotoxicity screening of MSI complexes disclosed that both CuSI and CdSI exhibited higher activity against human liver (Hep-G2) and breast (MDA-MB231) carcinoma cell lines than the reference (cisplatin) drug. The satisfactory bioactivities observed for several of these compounds supports the underlying design idea for combining important bioactive motifs for possible therapeutic benefit.

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Indoleamine 2,3-dioxygenase 1-mediated iron metabolism in macrophages contributes to lipid deposition in nonalcoholic steatohepatitis

Wu,

Li,

Jia

et al. 2024

J Gastroenterol

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The iron chelating agent, deferoxamine detoxifies Fe(Salen)-induced cytotoxicity

Cited by 49 publications

References 26 publications

Simultaneous hyperthermia‐chemotherapy effect by arterial injection of Fe(Salen) for femur tumor

Simultaneous hyperthermia‐chemotherapy effect by arterial injection of Fe(Salen) for femur tumor

Synthesis, Characterization, Theoretical Studies, and Antimicrobial/Antitumor Potencies of Salen and Salen/Imidazole Complexes of Co (II), Ni (II), Cu (II), Cd (II), Al (III) and La (III)

Indoleamine 2,3-dioxygenase 1-mediated iron metabolism in macrophages contributes to lipid deposition in nonalcoholic steatohepatitis

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