| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1317933 | Journal of Inorganic Biochemistry | 2010 | 7 Pages |
Platinum-based anticancer drugs such as cisplatin induce increased oxidative stress and oxidative damage of DNA and other cellular components, while selenium plays an important role in the antioxidant defense system. In this study, the interaction between a platinum(II) methionine (Met) complex [Pt(Met)Cl2] and a diselenide compound selenocystine [(Sec)2] was studied by electrospray ionization mass spectrometry, high performance liquid chromatography mass spectrometry, and 1H NMR spectroscopy. The results demonstrate that the diselenide bond in (Sec)2 can readily and quickly be cleaved by the platinum complex. Formation of the selenocysteine (Sec) bridged dinuclear complex [Pt2(Met-S,N)2(μ-Sec-Se,Cl)]3+ and Sec chelated species [Pt(Met-S,N)(Sec-Se,N)]2+ was identified at neutral and acidic media, which seems to result from the intermediate [Pt(Met-S,N)(Sec-Se)Cl]+. An accelerated formation of S–Se and S–S bonds was also observed when (Sec)2 reacted with excessive glutathione in the presence of [Pt(Met)Cl2]. These results imply that the mechanism of activity and toxicity of platinum drugs may be related to their fast reaction with seleno-containing biomolecules, and the chemoprotective property of selenium agents against cisplatin-induced toxicity could also be connected with such reactions.
Graphical abstractDiselenide can be readily cleaved by platinum complex, which may relate to the therapeutic and protective mechanism of platinum drugs.Figure optionsDownload full-size imageDownload as PowerPoint slide
