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Platinum analogue trans-[PtCl 2<br />
(3-Hmpy) 2<br />
] has high antitumor<br />
effectiveness against different tumor types<br />
Maja Čemažar1, Sabina Grabner2, Simona Kranjc1, Mira Lavrič1, Gregor Serša1, Nataša<br />
Bukovec2<br />
1Institute <strong>of</strong> Oncology Ljubljana, Dept. <strong>of</strong> Experimental Oncology, Zaloska 2, SI-1000 Ljubljana,<br />
Slovenia; 2Faculty <strong>of</strong> Chemistry and Chemical Technology, University <strong>of</strong> Ljubljana, Aškerčeva 5, 1000<br />
Ljubljana, Slovenia<br />
Although cisplatin is a valuable antitumor drug for treating several malignancies, it has<br />
several disadvantages including severe side effects and acquired drug resistance. The<br />
synthesis <strong>of</strong> new platinum complexes is aimed to overcome resistance to cisplatin and<br />
lower the side effects. The aim <strong>of</strong> our study was to determine the antitumor effectiveness<br />
<strong>of</strong> Pt(II) complex with 3-hydroxymethylpyridine (3-Hmpy) trans-[PtCl2(3-Hmpy)2] (S2)<br />
in comparison with cisplatin.<br />
We studied the interactions <strong>of</strong> S2 and cisplatin with plasmid DNA by gel electrophoresis.<br />
In addition, we determined the cytotoxicity <strong>of</strong> S2 on parental and cisplatin resistant<br />
ovarian carcinoma and bladder carcinoma cells by clonogenic assay and the antitumor<br />
effectiveness <strong>of</strong> intratumoral drug administration in solid tumors in mice.<br />
Analysis <strong>of</strong> undigested plasmid DNA electrophoretograms after treatment with S2 and<br />
cisplatin demonstrated that S2 compound caused less fast running supercoiled form<br />
and more singly nicked form band compared to cisplatin. In addition, with increasing<br />
concentrations S2 prevented BamH1 digestion <strong>of</strong> plasmid DNA indicating on change in<br />
DNA conformation, which was more pronounced than in the case <strong>of</strong> cisplatin.<br />
Bladder carcinoma cells and ovarian carcinoma cells resistant to cisplatin were equally<br />
sensitive to complex S2 in comparison to cisplatin. The parental ovarian carcinoma cells,<br />
which are intrinsically very sensitive to cisplatin were less sensitive to complex S2 compared<br />
to cisplatin.<br />
p10<br />
Growth <strong>of</strong> subcutaneous tumors after treatment with S2 was less delayed than<br />
after treatment with cisplatin in both tumor types.<br />
The results <strong>of</strong> our study demonstrate that S2 causes considerable damage to isolated DNA<br />
and is highly cytotoxic for cells, however, the antitumor effectiveness in solid tumors is<br />
less evident.<br />
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