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Apoptotic and chemotherapeutic properties of iron(III)-salophene in an ovarian cancer animal model

Lange, TS and McCourt, C and Singh, RK and Kyu, KK and Singh, AP and Luisi, BS and Alptürk, O and Strongin, RM and Brard, L (2009) Apoptotic and chemotherapeutic properties of iron(III)-salophene in an ovarian cancer animal model. Drug Design, Development and Therapy (3). 17 - 26.

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Abstract

The cytotoxicity of organometallic compounds iron(III)-, cobalt(III)-, manganese(II)-, and copper(II)-salophene (-SP) on platinum-resistant ovarian cancer cell lines was compared. Fe-SP displayed selective cytotoxicity (IC 50 at ∼1 μM) against SKOV-3 and OVCAR-3 cell lines while Co-SP caused cytotoxic effects only at higher concentrations (IC50 at 60 ?M) and Cu-SP effects were negligible. High cytotoxicity of Mn-SP (30-60 μM) appeared to be nonspecific because the Mn-chloride salt reduced cell viability similarly. The effect of Fe-SP at 1 μM proved to be ovarian cancer cell selective when compared to a panel of cell lines derived from different tumors. The first irreversible step in the induction of cell death by Fe-SP occurred after 3 hrs as indicated by the mitochondrial transmembrane potential (ΔΨm) and was mainly linked to apoptotic, not necrotic events. To evaluate the toxicity of Fe-SP in vivo we conducted an acute toxicity study in rats. The LD 50 of Fe-SP is >2000 mg/kg orally and >5.5 mg/kg body weight by intraperitoneal injection. An ovarian cancer animal model showed that the chemotherapeutic relevant dose of Fe-SP in rats is 0.5-1 mg/kg body weight. The present report suggests that Fe-SP is a potential therapeutic drug to treat ovarian cancer. © 2009 Lange et al, publisher and licensee Dove Medical Press Ltd.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Lange, TS
McCourt, C
Singh, RK
Kyu, KK
Singh, AP
Luisi, BS
Alptürk, O
Strongin, RM
Brard, L
Date: 1 October 2009
Date Type: Publication
Journal or Publication Title: Drug Design, Development and Therapy
Number: 3
Page Range: 17 - 26
Schools and Programs: School of Medicine > Medicine
Refereed: Yes
Date Deposited: 17 Dec 2012 18:53
Last Modified: 29 Jan 2019 15:55
URI: http://d-scholarship.pitt.edu/id/eprint/16894

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