The role of metal coordination complexes in cytosolic cellular defense

Abstract

The metal coordination complexes are known to induce cytotoxic effects on various cell lines and shown to have great potential for therapeutic interventions. Their main mechanism of action is through the mediation of enzyme activities in signaling pathways essential for cellular functioning. The overall cellular responses are dose-dependent and require high exposure levels and duration to overcome cellular defense against external toxicants. However, their effect through signal transduction components is limited due to the conferred drug resistance associated with glutathione transferase (GST)-mediated mechanisms. The GST family of enzymes is not only related to anticancer drug resistance, but also associated with cancer development where they may also contribute kinase signaling events including non-receptor protein tyrosine kinase (PTK)-related pathways. In the current study, we evaluated the effect of symmetrical and mononuclear complexes of Pd(II), Pt(II), and Ni(II) with organic ligands on cytosolic targets involved in glutathione utilization, antioxidant defense, and kinase signaling by virtue of acellular in vitro analyses.

Metabolic Aspects of Palladium(II) Potential Anti-Cancer Drugs

“…, DNA). In the same year, a comprehensive study of Pd(diethyl-dithiocarbamate) 2 , compared to its Pt(II) analogue and other symmetrical mononuclear Pt(II) and Ni(II) complexes ( 24 ), on human leukemia cells (K562 cell line) revealed detailed information on glutathione utilization, antioxidant mechanisms and kinase signaling, aiming at investigating the impact on cellular defense mechanisms. Figure 1 shows part of the different cellular defense mechanisms believed to be triggered by cisplatin, for instance, and correlate to development of drug resistance.…”

“… The coordination mechanism of Pt(II)-derived drug cDDP (cisplatin) with GSH and the consequent effect of GST-mediated drug resistance. Adapted from reference ( 24 ). …”