Cellular accumulation and DNA platination of two new platinum(II) anticancer compounds based on anthracene derivatives as carrier ligands |
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| Authors: | Patricia Marqués-Gallego Ulrich Jaehde Jaap Brouwer |
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| Institution: | a Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands
b Institute of Pharmacy, Clinical Pharmacy, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany |
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| Abstract: | The anticancer properties of two new fluorescent platinum(II) compounds, cis-Pt(A9opy)Cl2] and cis-Pt(A9pyp)(dmso)Cl2] are described. These compounds are highly active against several human tumor cell lines, including human ovarian carcinoma sensitive and cisplatin-resistant cell lines (A2780 and A2780R). To study the cellular processing of these new compounds, a series of in vitro studies have been performed, including the investigation of intracellular platinum accumulation and DNA-platination experiments in A2780 and A2780R cells. Compared to cisplatin, both compounds are accumulated highly in both sensitive and resistant cell lines, and more platinum has been found to bind to the nuclear DNA. Interestingly, cis-Pt(A9opy)Cl2] shows high accumulation and DNA adduct formation in the resistant cell line A2780R, as compared to the sensitive counterpart A2780 cell line. This suggests that cis-Pt(A9opy)Cl2] is able to overcome some of the well-known resistance mechanisms in this cell line, such as decreased cellular uptake and increased DNA repair. |
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| Keywords: | Platinum(II) compounds Short-time exposure cytotoxicity Platinum accumulation DNA platination Cisplatin-resistance |
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