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

Download Article [PDF] 

Creative Commons License This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution - Non Commercial (unported, v3.0) License. The full terms of the License are available at Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at:

Readers of this article also read:

PTEN insufficiency modulates ER+ breast cancer cell cycle progression and increases cell growth in vitro and in vivo

Chiang KC, Chen HY, Hsu SY, Pang JHS, Wang SY, Hsu JT, Yeh TS, Chen LW, Kuo SF, Sun CC, Lee JM, Yeh CN, Juang HH

Drug Design, Development and Therapy 2015, 9:4631-4638

Published Date: 13 August 2015

Safety of inhaled glycopyrronium in patients with COPD: a comprehensive analysis of clinical studies and post-marketing data

D’Urzo AD, Kerwin EM, Chapman KR, Decramer M, DiGiovanni R, D’Andrea P, Hu H, Goyal P, Altman P

International Journal of Chronic Obstructive Pulmonary Disease 2015, 10:1599-1612

Published Date: 11 August 2015

Lobar analysis of collapsibility indices to assess functional lung volumes in COPD patients

Kitano M, Iwano S, Hashimoto N, Matsuo K, Hasegawa Y, Naganawa S

International Journal of Chronic Obstructive Pulmonary Disease 2014, 9:1347-1356

Published Date: 9 December 2014

Experimental study of tissue-engineered cartilage allograft with RNAi chondrocytes in vivo

Wang ZH, Li XL, He XJ, Zhang XH, Yang ZQ, Xu M, Wu BJ, Tu JB, Luo HN, Yan J

Therapeutics and Clinical Risk Management 2014, 10:335-340

Published Date: 8 May 2014

Profile of ocriplasmin and its potential in the treatment of vitreomacular adhesion

Stefanini FR, Maia M, Falabella P, Pfister M, Niemeyer M, Kashani AH, Humayun MS, Koss MJ

Clinical Ophthalmology 2014, 8:847-856

Published Date: 6 May 2014

Applanation tonometry: a comparison of the Perkins handheld and Goldmann slit lamp-mounted methods

Arora R, Bellamy H, Austin MW

Clinical Ophthalmology 2014, 8:605-610

Published Date: 26 March 2014

Sustained effect of resistance training on blood pressure and hand grip strength following a detraining period in elderly hypertensive women: a pilot study

Nascimento D da C, Tibana RA, Benik FM, Fontana KE, Neto FR, de Santana FS, Santos-Neto L, Silva RAS, Silva AO, Farias DL, Balsamo S, Prestes J

Clinical Interventions in Aging 2014, 9:219-225

Published Date: 20 January 2014