Back to Browse Journals » Drug Design, Development and Therapy » Volume 3

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

Authors Thilo S Lange, Carolyn McCourt, Rakesh K Singh, Kyu Kwang Kim, Ajay P Singh, et al

Published 17 December 2008 Volume 2009:3 Pages 17—26


Review by Single-blind

Peer reviewer comments 2

Thilo S Lange1,2, Carolyn McCourt2, Rakesh K Singh2, Kyu Kwang Kim2, Ajay P Singh3, Brian S Luisi4, Onur Alptürk5, Robert M Strongin6, Laurent Brard2

1Division of Biology and Medicine Brown University, Providence, R1, USA; 2Molecular Therapeutics Laboratory, Program in Women’s Oncology, Department of Obstetrics and Gynecology, Women and Infants’ Hospital of RI, Warren Alpert Medical School of Brown University, Providence, RI, USA; 3Department of Plant Biology, Rutgers University, New Brunswick, NJ, USA; 4Department of Chemistry, Brown University, Providence, RI, USA; 5Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; 6Department of Chemistry, Portland State University, Portland, OR, USA

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 (IC50 at ∼1 μM) against SKOV-3 and OVCAR-3 cell lines while Co-SP caused cytotoxic effects only at higher concentrations (IC50 at 60 μM) 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 LD50 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.

Keywords: iron(III)-salophene, chemotherapeutic properties, p38 MAPK, ovarian cancer animal model

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF] 


Readers of this article also read:

Factors associated with group bullying and psychopathology in elementary school students using child-welfare facilities

Kim JW, Lee K, Lee YS, Han DH, Min KJ, Song SH, Park GN, Lee JY, Kim JO

Neuropsychiatric Disease and Treatment 2015, 11:991-998

Published Date: 7 April 2015

Adherence and rehospitalizations in patients with schizophrenia: evidence from Japanese claims data

Kuwabara H, Saito Y, Mahlich J

Neuropsychiatric Disease and Treatment 2015, 11:935-940

Published Date: 1 April 2015

Efficacy and safety of once-daily glycopyrronium in predominantly Chinese patients with moderate-to-severe chronic obstructive pulmonary disease: the GLOW7 study

Wang C, Sun T, Huang Y, Humphries M, Bai L, Li L, Wang Q, Kho P, Firth R, D’Andrea P

International Journal of Chronic Obstructive Pulmonary Disease 2015, 10:57-68

Published Date: 5 January 2015

MRI-based identification of undifferentiated cells: looking at the two faces of Janus

Tomuleasa C, Florian IS, Berce C, Irimie A, Berindan-Neagoe I, Cucuianu A

International Journal of Nanomedicine 2014, 9:865-866

Published Date: 11 February 2014

Reducing dropout of contact lens wear with Biotrue multipurpose solution

Rah MJ, Merchea MM, Doktor MQ

Clinical Ophthalmology 2014, 8:293-299

Published Date: 24 January 2014

Performance of Cpred/Cobs concentration ratios as a metric reflecting adherence to antidepressant drug therapy

Yan Feng, Marc R Gastonguay, Bruce G Pollock, et al

Neuropsychiatric Disease and Treatment 2011, 7:117-125

Published Date: 17 March 2011

Efficacy and safety of travoprost/timolol vs dorzolamide/timolol in patients with open-angle glaucoma or ocular hypertension

Miguel A Teus, Stefano Miglior, Guna Laganovska, et al

Clinical Ophthalmology 2009, 3:629-636

Published Date: 13 November 2009