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- Title
Iron(III)-Salophene: An Organometallic Compound with Selective Cytotoxic and Anti-Proliferative Properties in Platinum-Resistant Ovarian Cancer Cells.
- Authors
Lange, Thilo S.; Kyu Kwang Kim; Singh, Rakesh K.; Strongin, Robert M.; McCourt, Carolyn K.; Brard, Laurent
- Abstract
Background: In this pioneer study to the biological activity of organometallic compound Iron(III)-salophene (Fe-SP) the specific effects of Fe-SP on viability, morphology, proliferation, and cell-cycle progression on platinum-resistant ovarian cancer cell lines were investigated. Methodology/Principal Findings: Fe-SP displayed selective cytotoxicity against SKOV-3 and OVCAR-3 (ovarian epithelial adenocarcinoma) cell lines at concentrations between 100 nM and 1 μM, while the viability of HeLa cells (epithelial cervix adenocarcinoma) or primary lung or skin fibroblasts was not affected. SKOV-3 cells in contrast to fibroblasts after treatment with Fe-SP revealed apparent hallmarks of apoptosis including densely stained nuclear granular bodies within fragmented nuclei, highly condensed chromatin and chromatin fragmentation. Fe-SP treatment led to the activation of markers of the extrinsic (Caspase-8) and intrinsic (Caspase-9) pathway of apoptosis as well as of executioner Caspase-3 while PARP-1 was deactivated. Fe-SP exerted effects as an anti-proliferative agent with an IC50 value of 300 nM and caused delayed progression of cells through S-phase phase of the cell cycle resulting in a complete S-phase arrest. When intra-peritoneally applied to rats Fe-SP did not show any systemic toxicity at concentrations that in preliminary trials were determined to be chemotherapeutic relevant doses in a rat ovarian cancer cell model. Conclusion/Significance: The present report suggests that Fe-SP is a potent growth-suppressing agent in vitro for cell lines derived from ovarian cancer and a potential therapeutic drug to treat such tumors in vivo.
- Subjects
CANCER cells; OVARIAN diseases; CELL proliferation; ADENOCARCINOMA; CELL morphology; FIBROBLASTS; APOPTOSIS; CELL lines; TUMOR treatment; PATIENTS; CANCER
- Publication
PLoS ONE, 2008, Vol 3, Issue 5, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0002303