Sponsor
RGM is partially supported by NCI Grant #1 RO1 CA136491-01 and Grants from Swim Across America. RKS is partially supported by Grants from Swim Across America.
Published In
PLoS ONE
Document Type
Article
Publication Date
4-2011
Subjects
Cell-mediated cytotoxicity, Cell proliferation, Tumors in children, Ovaries -- Cancer
Abstract
The objective of the present study was to investigate the specific effects of Iron(III)-salophene (Fe-SP) on viability, morphology, proliferation, cell cycle progression, ROS generation and pro-apoptotic MAPK activation in neuroblastoma (NB) cells. A NCI-DTP cancer screen revealed that Fe-SP displayed high toxicity against cell lines of different tumor origin but not tumor type-specificity. In a viability screen Fe-SP exhibited high cytotoxicity against all three NB cell lines tested. The compound caused cell cycle arrest in G1 phase, suppression of cells progressing through S phase, morphological changes, disruption of the mitochondrial membrane depolarization potential, induction of apoptotic markers as well as p38 and JNK MAPK activation, DNA degradation, and elevated generation of reactive oxygen species (ROS) in SMS-KCNR NB cells. In contrast to Fe-SP, non-complexed salophene or Cu(II)-SP did not raise ROS levels in NB or SKOV-3 ovarian cancer control cells. Cytotoxicity of Fe-SP and activation of caspase-3, -7, PARP, pro-apoptotic p38 and JNK MAPK could be prevented by co-treatment with antioxidants suggesting ROS generation is the primary mechanism of cytotoxic action. We report here that Fe-SP is a potent growth-suppressing and cytotoxic agent for in vitro NB cell lines and, due to its high tolerance in previous animal toxicity studies, a potential therapeutic drug to treat NB tumors in vivo.
DOI
10.1371/journal.pone.0019049
Persistent Identifier
http://archives.pdx.edu/ds/psu/11115
Citation Details
Kyu Kwang, K., Singh, R. K., Strongin, R. M., Moore, R. G., Brard, L., & Lange, T. S. (2011). Organometallic Iron(III)-Salophene Exerts Cytotoxic Properties in Neuroblastoma Cells via MAPK Activation and ROS Generation. Plos ONE, 6(4), 1-10. doi:10.1371/journal.pone.0019049
Description
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© 2011 Kim et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.