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

Thilo S. Lange, Carolyn McCourt, Rakesh K. Singh, Kwang Kim Kyu, Ajay P. Singh, Brian S. Luisi, Onur Alptürk, Robert M. Strongin, Laurent Brard*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)17-26
Number of pages10
JournalDrug Design, Development and Therapy
Issue number3
Publication statusPublished - 2009
Externally publishedYes

Keywords

  • Chemotherapeutic properties
  • Iron(III)-salophene
  • Ovarian cancer animal model
  • p38 MAPK

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