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

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 muM) against SKOV-3 and OVCAR-3 cell lines while Co-SP caused cytotoxic effects only at higher concentrations (IC(50) at 60 muM) and Cu-SP effects were negligible. High cytotoxicity of Mn-SP (30-60 muM) appeared to be nonspecific because the Mn-chloride salt reduced cell viability similarly. The effect of Fe-SP at 1 muM 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 (DeltaPsim) 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.
AuthorsThilo S Lange, Carolyn McCourt, Rakesh K Singh, Kyu Kwang Kim, Ajay P Singh, Brian S Luisi, Onur Alptürk, Robert M Strongin, Laurent Brard
JournalDrug design, development and therapy (Drug Des Devel Ther) Vol. 3 Pg. 17-26 (Sep 21 2009) ISSN: 1177-8881 [Electronic] New Zealand
PMID19920918 (Publication Type: Journal Article)

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