Iron(III)-Salophene: An Organometallic Compound with Selective Cytotoxic and Anti-Proliferative Properties in Platinum-Resistant Ovarian Cancer Cells

Abstract

BackgroundIn 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 FindingsFe-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/SignificanceThe 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.

Purified cranberry proanthocyanidines (PAC-1A) cause pro-apoptotic signaling, ROS generation, cyclophosphamide retention and cytotoxicity in high-risk neuroblastoma cells

“…SMS-KCNR cells exhibit a uniform phenotype with small, round N-type cells that have short neuritic processes (34). This cell line was chosen as a model for mechanistic experiments in the current report since they display MYCN amplification, express caspase-8 (35) and apoptosis can be mediated through the intrinsic as well as extrinsic pathway (36). PAC-1A, however, induced cell death of SMS-KCNR through both apoptotic pathways via: i) modulation of expression of these mitochondrial Bcl-2 family proteins with pro-survival (Bcl-2, Bcl-xL) or pro-apoptotic (Bax, Bad, Bid) function, ii) TNF-family regulated extrinsic/death receptor signaling, and iii) activation of pro-apoptotic MAPK (e.g., SAPK/JNK) and suppression of pro-survival signaling through the PI3K/AKT/mTOR pathway.…”

Coordination compounds in cancer: Past, present and perspectives

“…Also complexes with ferrocene (ferrocifenes) show anticancer activity, with a selectivity that depends on the present substituents. Several hydroxy-substituted ferrocifens present high affinity with oestrogen receptor and are used for the treatment of breast cancer (Lange et al, 2008;Rafique et al, 2010). Interestingly, the ferrocene alone does not show anticancer activity.…”

Description of the cytotoxic effect of a novel drug Abietyl-Isothiocyanate on endometrial cancer cell lines

“…Cell viability assay Viability of cell lines was determined by the CellTiter 96® Aqueous One Solution Assay (Promega Corp, Madison, WI) following the manufacturer's recommendations with suitable modifications [17]. Briefly, cells were seeded into a 96-well microtiter plate at 1×10 4 cells/100 μl per well and treated in complete medium as indicated for 24 h. During the last 4 h of incubation the MTS reagent was added at a 1:10 dilution to the medium.…”