Copper(II) Bis(diethyldithiocarbamate) Induces the Expression of Syndecan-4, a Transmembrane Heparan Sulfate Proteoglycan, via p38 MAPK Activation in Vascular Endothelial Cells.

Proteoglycans synthesized by vascular endothelial cells are important for regulating cell function and the blood coagulation-fibrinolytic system. Since we recently reported that copper(II) bis(diethyldithiocarbamate) (Cu(edtc)2) modulates the expression of some molecules involving the antioxidant and blood coagulation systems, we hypothesized that Cu(edtc)2 may regulate the expression of proteoglycans and examined this hypothesis using a bovine aortic endothelial cell culture system. The experiments showed that Cu(edtc)2 induced the expression of syndecan-4, a transmembrane heparan sulfate proteoglycan, in a dose- and time-dependent manner. This induction required the whole structure of Cu(edtc)2-the specific combination of intramolecular copper and a diethyldithiocarbamate structure-as the ligand. Additionally, the syndecan-4 induction by Cu(edtc)2 depended on the activation of p38 mitogen-activated protein kinase (MAPK) but not the Smad2/3, NF-E2-related factor2 (Nrf2), or epidermal growth factor receptor (EGFR) pathways. p38 MAPK may be a key molecule for inducing the expression of syndecan-4 in vascular endothelial cells.

Recent advances in ruthenium and platinum based supramolecular coordination complexes for antitumor therapy.

Since the discovery of cisplatin for antitumor activity, the platinum (Pt) based antitumor drugs have received significant attention and launched a new era to explore the transition metal complexes for therapy. However, these small Pt-based antitumor drugs have some limitations for their clinic application, such as short blood circulation time and limited accumulation at tumor site, which was mainly due to their poor water solubility and small molecule size. To overcome these obstacles, developing new generation of transition-metal based complexes as anticancer agents is urgently needed. For the unique properties, the ruthenium (Ru) based complexes have attractive significant attention and be expected to be a substitute for Pt-based anticancer agents. Due to the nanometer size, unique geometry, relatively high surface charge and unique photophysical properties, the transition-metal based supramolecular coordination complexes (SCCs) which exhibited excellent antitumor efficiency and possessed desirable bioapplications such as drug loading, bioimaging and biosensing have attracted great attention as anticancer agents. In this minireview, we will highlight the recent development of ruthenium (Ru) and Platinum (Pt) based SCCs as potential anticancer agents.