Light-Activated Destruction of Cancer Cell Nuclei by Platinum Diazide Complexes
2006; Elsevier BV; Volume: 13; Issue: 1 Linguagem: Inglês
10.1016/j.chembiol.2005.10.011
ISSN1879-1301
AutoresPatrick J. Bednarski, Renate Grünert, Michael Zielzki, Anja Wellner, Fiona Mackay, Peter J. Sadler,
Tópico(s)DNA and Nucleic Acid Chemistry
ResumoA possible way to avoid dose-limiting side effects of platinum anticancer drugs is to employ light to cause photochemical changes in nontoxic platinum prodrugs that release active antitumor agents. This strategy could be used in the treatment of localized cancers accessible to irradiation (e.g., bladder, lung, esophagus, and skin). We report here that nontoxic photolabile diam(m)ino platinum(IV) diazido complexes inhibit the growth of human bladder cancer cells upon irradiation with light, and are non-crossresistant to cisplatin. Their rate of photolysis closely parallels that of DNA platination, indicating that the photolysis products interact directly, and rapidly, with DNA. Photoactivation results in a dramatic shrinking of the cancer cells, loss of adhesion, packing of nuclear material, and eventual disintegration of their nuclei, indicating a different mechanism of action from cisplatin.
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