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

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

Brown University
Women and Infants Hospital of Rhode Island
Rutgers - The State University of New Jersey, New Brunswick
University of Pittsburgh
Portland State University
Division of Gynecologic Oncology

Research output: Contribution to journal › Article › peer-review

23 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 language	English
Pages (from-to)	17-26
Number of pages	10
Journal	Drug Design, Development and Therapy
Issue number	3
Publication status	Published - 2009
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

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

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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 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.",

keywords = "Chemotherapeutic properties, Iron(III)-salophene, Ovarian cancer animal model, p38 MAPK",

author = "Lange, \{Thilo S.\} and Carolyn McCourt and Singh, \{Rakesh K.\} and Kyu, \{Kwang Kim\} and Singh, \{Ajay P.\} and Luisi, \{Brian S.\} and Onur Alpt{\"u}rk and Strongin, \{Robert M.\} and Laurent Brard",

year = "2009",

language = "English",

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journal = "Drug Design, Development and Therapy",

issn = "1177-8881",

publisher = "Dove Medical Press Ltd.",

number = "3",

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TY - JOUR

T1 - Apoptotic and chemotherapeutic properties of iron(III)-salophene in an ovarian cancer animal model

AU - Lange, Thilo S.

AU - McCourt, Carolyn

AU - Singh, Rakesh K.

AU - Kyu, Kwang Kim

AU - Singh, Ajay P.

AU - Luisi, Brian S.

AU - Alptürk, Onur

AU - Strongin, Robert M.

AU - Brard, Laurent

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

KW - Chemotherapeutic properties

KW - Iron(III)-salophene

KW - Ovarian cancer animal model

KW - p38 MAPK

UR - https://www.scopus.com/pages/publications/77949886671

M3 - Article

AN - SCOPUS:77949886671

SN - 1177-8881

SP - 17

EP - 26

JO - Drug Design, Development and Therapy

JF - Drug Design, Development and Therapy

IS - 3

ER -

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

Abstract

UN SDGs

Keywords

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