Book of Abstracts - Ruhr-Universität Bochum

P-29
ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum
Transcriptional Profile of HT-29 Cells upon Treatment with Different
Organometallic Compounds
Igor Kitanovic, a Ana Kitanovic, a Hamed Alborzinia, a Suzan Can, a Pavlo Holenya, a Elke Lederer, a
Hans-Günther Schmalz, b Annegret Hille, c Ronald Gust, c Ingo Ott, d Aram Prokop, e Melanie Oleszak, f
Yvonne Geldmacher, f William S. Sheldrick, f Gilles Gasser, g Nils Metzler-Nolte, h and Stefan Wölfl* a
a Institute of Pharmacy and Molecular Biotechnology, University Heidelberg, Germany, b Institute of
Inorganic Chemistry, University of Cologne, Germany, c Institute of Pharmacy, Department of
Pharmaceutical Chemistry, Freie Universität Berlin, Germany, d Institute of Pharmaceutical
Chemistry, Technische Universität Braunschweig, Germany, e Cologne City Hospital, Department of
Oncology, Cologne, Germany, f Faculty of Chemistry and Biochemistry, Department of Analytical
Chemistry, University Bochum, g Institute of Inorganic Chemistry, University of Zurich, h Faculty of
Chemistry and Biochemistry, Department of Bioinorganic Chemistry, University of Bochum
email: Igor.Kitanovic@urz.uni-heidelberg.de, wolfl@uni-hd.de
In the past several decades metal compounds containing platinum became an essential part of many
clinical protocols for anti-cancer therapy. Considered to be relatively unspecific compounds that block
DNA-replication and cell cycle progression, metal-containing compounds were not in the research
focus of medicinal chemistry. New developments in the chemistry of (bio-)organometallic compounds
however lead to the discovery of several unexpected highly specific activities of new organometallic
compounds and opened new important perspectives in this field.
For cancer therapy cancer cell specific toxicity and apoptosis induction are highly desirable features of
new potential drugs. Within our collaborative network a wide range of new (bio-)orgamometallic
compounds were developed that show very distinct cytotoxic properties suggesting that rather than
acting through a common mechanism different cellular targets are responsible for cytotoxicity and cell
death induction.
We will present a comprehensive analysis of the cellular response of human colorectal
adenocarcinoma cells HT29 with very diverse organometallic compounds: ranging from FeIIsalophenes,
through more classical bioorganometallic compounds to bioorganometallic compounds
derived from established (non-metal containing) drugs. To elucidate their specific activity profile,
standard cell based assays were combined with genome wide gene expression profiling using
affymetrix gene expression arrays. Although the substances represent a wide range of different
structures and metal cores, they all are highly cytotoxic and clearly induce apoptosis in HT-29 cells.
For gene expression profiling concentrations just below the IC50 (cytotoxicity) were chosen to obtain
more compound specific alterations in gene expression rather then common cytotoxicity profiles, in
addition mRNAs were collected at different time points critical in the cellular response upon
treatment.
The results obtained show similar response characteristics, but also very compound specific changes.
This clearly indicates very distinct biological properties and suggests common response mechanisms
as well as high selectivity and target specificity.
List of compounds: Hi41, CoASS (AG Gust), MH1 (AG Scheldrick), MeN69 (AG Schmaltz),
FcOHTAM3, ReGG1 (AG Metzler-Nolte)
This work is supported by the DFG as part of the Forschergruppe FOR630.
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