Light-activated destruction of cancer cell nuclei by platinum diazide complexes.
A 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.
Bednarski
Patrick J
PJ
Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, University of Greifswald, Germany. bednarsk@uni-greifswald.de
Grünert
Renate
R
Zielzki
Michael
M
Wellner
Anja
A
Mackay
Fiona S
FS
Sadler
Peter J
PJ
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001386:Azides / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects* / Q000528:radiation effects*; D004247:DNA / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008027:Light; D015394:Molecular Structure; D009369:Neoplasms / Q000473:pathology*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D010984:Platinum / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013057:Spectrum Analysis; D013696:Temperature
D000970:Antineoplastic Agents; D001386:Azides; D017319:Photosensitizing Agents; D010984:Platinum; D004247:DNA