The molecular mechanisms of antimetastatic ruthenium compounds explored through DIGE proteomics

New Insights into the Molecular Mechanisms of Selected Anticancer Metal Compounds through Bioinformatic Analysis of Proteomic Data

“…The second correlation we found was between two proteins involved in connections of cytoskeletal components to membrane: the protein Ubiquilin-1 and the protein Ezrin. In our recent paper, we reported that two ruthenium compounds caused proteomic alterations, and we found that 9 proteins are in common between RAPTA-T and NAMI-A, implying that their respective mechanisms are highly correlated [18]. Analysis of all these proteins by PPI Spider resulted a significant network model, indicating two classes of proteins correlated to each other and belonging to: i) Apoptosis, cellular proliferation and DNA stability, and ii) Cytoskeleton dynamics, splicing regulation and protein biosynthesis.…”

“…In our network, we found GAPDH connected with the Peroxiredoxin-1 (Q 06830) [2,18], identified by previous proteomic analysis, which is involved in redox regulation of the cell. Recently, Maller et al [33], found that GAPDH's oxidation state controls the protein biosynthesis, and its nitrosylation state is important to induce apoptosis.…”

“…The SMN2 protein plays an essential role in spliceosomal assembly, and is required for pre-mRNA splicing [29]. Moreover, an intermediate node which connects the two elongation factors, previously identified by proteome analysis (Elongation factor 1-beta -P24534 [1] and Elongation factor 1-delta -P29692 [18], is the Elongation factor 1 -alpha 2 (EEF1A2-Q05639). These components of the eEF1 complex have the canonical functions in translation elongation [30], and many noncanonical functions, including roles in nuclear export events, turnover of misfolded proteins, binding and bundling of the actin cytoskeleton and apoptosis.…”

“…In a very recent paper, we have used for the first time, 2D-DIGE to investigate the mode of action of two anticancer ruthenium compounds, namely NAMI-A and RAPTA-T in A2780/S human cancer cells [18]. Changes in the expression of intracellular proteins after the treatment at non-cytotoxic concentrations were monitored.…”

Ruthenium(II)/4,6-dimethyl-2-mercaptopyrimidine complexes: Synthesis, characterization, X-ray structures and in vitro cytotoxicity activities on cancer cell lines

“…The success of cisplatin, carboplatin and oxaliplatin as anticancer agents has stimulated the search for cytotoxic of transition metal compounds with more acceptable toxicity profile and expansion of activity [2,7,8]. In this sense other classes of metal compounds, the potential non platinum metallodrugs, have been developed and extensively investigated in the search of new anticancer drugs [9,10]. Some of these compounds have showed a promising activity, with biological features, which are very different from those of classical platinum compounds [11][12][13].…”