title: 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.
authors.affiliation: Division of Biology and Medicine, Brown University, Providence, RI, USA.
authors.forename: Thilo S
authors.initials: TS
authors.lastname: Lange
authors.forename: Carolyn
authors.initials: C
authors.lastname: McCourt
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Singh
authors.forename: Kyu Kwang
authors.initials: KK
authors.lastname: Kim
authors.forename: Ajay P
authors.initials: AP
authors.lastname: Singh
authors.forename: Brian S
authors.initials: BS
authors.lastname: Luisi
authors.forename: Onur
authors.initials: O
authors.lastname: Alptürk
authors.forename: Robert M
authors.initials: RM
authors.lastname: Strongin
authors.forename: Laurent
authors.initials: L
authors.lastname: Brard