Journal
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
Volume 20, Issue 1, Pages 101-108Publisher
SPRINGER
DOI: 10.1007/s00775-014-1217-3
Keywords
Insulin-degrading enzyme; Cisplatin; Neuroblastoma; Platinum(II) compounds
Funding
- Italian Ministry of the University and Research [MiUR FIRB RBNE03PX83]
Ask authors/readers for more resources
The properties of three novel Platinum(II) compounds toward the insulin-degrading enzyme (IDE) enzymatic activity have been investigated under physiological conditions. The rationale of this study resides on previous observations that these compounds, specifically designed and synthesized by some of us, induce apoptosis in various cancer cell lines, whereas IDE has been proposed as a putative oncogene involved in neuroblastoma onset and progression. Two of these compounds, namely [PtCl(O,O'-acac)(DMSO)] and [Pt(O,O'-acac)(gamma-acac)(DMS)], display a modulatory behavior, wherefore activation or inhibition of IDE activity occurs over different concentration ranges (suggesting the existence of two binding sites on the enzyme). On the other hand, [Pt(O,O'-acac)(gamma-acac)(DMSO)] shows a typical competitive inhibitory pattern, characterized by a meaningful affinity constant (K (i) = 0.95 +/- A 0.21 mu M). Although all three compounds induce cell death in neuroblastoma SHSY5Y cells at concentrations exceeding 2 mu M, the two modulators facilitate cells' proliferation at concentrations a parts per thousand currency sign 1.5 mu M, whereas the competitive inhibitor [Pt(O,O'-acac)(gamma-acac)(DMSO)] only shows a pro-apoptotic activity at all investigated concentrations. These features render the [Pt(O,O'-acac)(gamma-acac)(DMSO)] a promising lead compound for the synthesis of IDE-specific inhibitors (not characterized yet) with therapeutic potentiality.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available