In vitro antitumour activity of water soluble Cu(I), Ag(I) and Au(I) complexes supported by hydrophilic alkyl phosphine ligands

Santini, Carlo; Pellei, Maura; Papini, Grazia; Morresi, Barbara; Galassi, Rossana; Ricci, Simone; Tisato, Francesco; Porchia, Marina; Rigobello, Maria Pia; Marzano, Cristina

doi:10.1016/j.jinorgbio.2010.10.016

Cited by 102 publications

(91 citation statements)

References 72 publications

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“…IC50 s (inhibitory concentrations) are used early in the discovery process to evaluate the suitability and the performance of drugs. The IC50 values reported in this work were typically determined after treated samples were incubated for 24 h. The IC50 concentrations of compounds 1-4 ranged from 3 to 3.59 lM (Table 2), comparable to, or much lower than that of CDDP (Table 2) other Ag(I) complexes (Berners-Price and Sadler 1988; Liu et al 2008;Santini et al 2011). The effect of the various ligands on the viability of the MCF-7 cells was studied in order to determine, by comparison, whether they showed any cytotoxic activity.…”

Section: Resultsmentioning

confidence: 68%

The effect of 1:2 Ag(I) thiocyanate complexes in MCF-7 breast cancer cells

et al. 2015

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There is much interest currently in the design of metal compounds as drugs and various metal compounds are already in clinical use. These include gold(I) compounds such as auranofin and the anti-cancer platinum(II) complex, cisplatin. Bis-chelated gold(I) phosphine complexes have also shown great potential as anticancer agents, however, their efficacy has been limited by their high toxicity. In this study, silver(I) thiocyanate compounds linked to four specific ligands, were synthesized and characterized. These silver-phosphine adducts included [AgSCN{P(4-MeC6H4)3}2]2 (1); [AgSCN{P(4-ClC6H4)3}2]2 (2); [AgSCN{P(4-MeOC6H4)3}2]2 (3); [AgSCN(PPh3)2]2 (4). The compounds were found to be toxic to MCF-7 breast cancer cells while the ligands on their own were not toxic. Our findings further indicate that the silver(I) phosphine compounds induce apoptotic cell death in these breast cancer cells. In addition, the compounds were not toxic to nonmalignant fibroblast cells at the IC50 concentrations. This is an indication that the compounds show selectivity towards the cancer cells.

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Section: Resultsmentioning

confidence: 68%

The effect of 1:2 Ag(I) thiocyanate complexes in MCF-7 breast cancer cells

et al. 2015

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“…The active site selenocysteine residue of TrxR has been shown to be sensitive to arsenic and gold compounds in recent years, and this reactivity has generated a great deal of interest in this enzyme as a target for cancer research and toxicology (Cox et al 2008; Ganyc et al 2007; Jackson-Rosario and Self 2010; Lu et al 2007; Meno et al 2009; Prast-Nielsen et al 2011; Santini et al 2011; Talbot et al 2008). Given the similarities with arsenic in the patterns in the results of exposure to Ag ions and the similar reactivity of hydrogen selenide to reduced selenocysteine residues, we speculated that TrxR1 might also be sensitive to Ag ions.…”

Section: Resultsmentioning

confidence: 99%

“…The selenocysteine active site of human TrxR has been shown to react with many different metals, metal–drug complexes, and metalloids (Cheng et al 2009; Eriksson et al 2009; Gandin et al 2010; Jackson-Rosario and Self 2010; Lu et al 2007; Prast-Nielsen et al 2010, 2011; Santini et al 2011). A large body of literature exists on studies of the differential sensitivity of TrxR to gold compounds (i.e., aurothioglucose, aurothiomalate, and auranofin) compared with Gpx and glutathione reductase (Nordberg and Arner 2001).…”

Section: Discussionmentioning

confidence: 99%

Exposure to Silver Nanoparticles Inhibits Selenoprotein Synthesis and the Activity of Thioredoxin Reductase

Srivastava

Singh

Self

2012

Environ Health Perspect

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Background: Silver nanoparticles (AgNPs) and silver (Ag)-based materials are increasingly being incorporated into consumer products, and although humans have been exposed to colloidal Ag in many forms for decades, this rise in the use of Ag materials has spurred interest into their toxicology. Recent reports have shown that exposure to AgNPs or Ag ions leads to oxidative stress, endoplasmic reticulum stress, and reduced cell proliferation. Previous studies have shown that Ag accumulates in tissues as silver sulfides (Ag2S) and silver selenide (Ag2Se).Objectives: In this study we investigated whether exposure of cells in culture to AgNPs or Ag ions at subtoxic doses would alter the effective metabolism of selenium, that is, the incorporation of selenium into selenoproteins.Methods: For these studies we used a keratinocyte cell model (HaCat) and a lung cell model (A549). We also tested (in vitro, both cellular and chemical) whether Ag ions could inhibit the activity of a key selenoenzyme, thioredoxin reductase (TrxR).Results: We found that exposure to AgNPs or far lower levels of Ag ions led to a dose-dependent inhibition of selenium metabolism in both cell models. The synthesis of protein was not altered under these conditions. Exposure to nanomolar levels of Ag ions effectively blocked selenium metabolism, suggesting that Ag ion leaching was likely the mechanism underlying observed changes during AgNP exposure. Exposure likewise inhibited TrxR activity in cultured cells, and Ag ions were potent inhibitors of purified rat TrxR isoform 1 (cytosolic) (TrxR1) enzyme.Conclusions: Exposure to AgNPs leads to the inhibition of selenoprotein synthesis and inhibition of TrxR1. Further, we propose these two sites of action comprise the likely mechanism underlying increases in oxidative stress, increases endoplasmic reticulum stress, and reduced cell proliferation during exposure to Ag.

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“…23 The study has been also extended to the complexation of Ag(I) by PTA since the Ag(I)/PTA complexes have also already been tested for their cytotoxicity. 11 Density Functional Theory (DFT) calculations have been employed to assess the nature and stoichiometry of the prevailing Cu(I) species in solution in the presence and absence of PTA. This computational approach has been successfully employed to obtain reliable structural and thermochemical data for metal complex formation in the gas phase and aqueous solution.…”

Section: Introductionmentioning

confidence: 99%