Due to a number of unpleasant considerations, marketed
drugs have
steadily lost their importance in the treatment of cancer. In order
to find a viable cancer cell diagnostic agent, we therefore focused
on metal complexes that displayed target adequacy, permeability to
cancer cells, high standard water solubility, cytoselectivity, and
luminescent behavior. In this aspect, luminescent 11-{naphthalen-1-yl}
dipyrido [3,2-a:2′,3′-c] phenazine based Ru(II)/Ir(III)/Re(I)
complexes have been prepared for HCT-116 colorectal cancer stem cell
therapy. Our study successfully established the possible cytotoxicity
of IrL complex at different doses on HCT-116 colorectal
cancer stem cells (CRCSCs). Additionally, an immunochemistry analysis
of the complex IrL showed that the molecule was subcellularly
localized in the nucleus and other regions of the cytoplasm, where
it caused nuclear DNA damage and mitochondrial dysfunction. The level
of BAX and Bcl-2 was further quantified by qRT-PCR. The expression
of proapoptotic BAX showed increased expression in the complex IrL-treated cell compared to the control, indicating the potential
of complex IrL for apoptotic induction. Upon further
validation, complex IrL was developed as an inhibitor
of autophagy for the eradication of cancer stem cells.
Herein, we have introduced a series of Iridium(III)-Cp*-imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenol complexes via a convenient synthetic methodology which acts as hypoxia active and Glutathione-resistant anticancer metallotherapeutics. Complex [IrIII(Cp*)(L5)(Cl)](PF6) (IrL5) exhibited best cytoselectivity, GSH...
Sodium Fluoride (NaF) can change the expression of skeletal muscle proteins. Since skeletal muscle is rich in mitochondrial and contractile (sarcomeric) proteins, these proteins are sensitive to the effects of NaF, and the changes are dose-and time-dependent. In the current study, we have analysed the effect of high concentrations of NaF (80ppm) on mouse skeletal muscle at two different time points, i.e., 15 days and 60 days. At the end of the experimental time, the animals were sacrificed, skeletal muscles were isolated, and proteins were extracted and subjected to bioinformatic (Mass Spectrometric) analysis. The results were analysed based on changes in different mitochondrial complexes, contractile (sarcomeric) proteins, 26S proteasome, and ubiquitin-proteasome pathway. The results showed that the mitochondrial proteins of complex I, II, III, IV and V were differentially regulated in the groups treated with 80ppm of NaF for 15 days and 60 days. The network analysis indicated more changes in mitochondrial proteins in the group treated with the higher dose for 15 days rather than 60 days. Furthermore, differential expression of (sarcomeric) proteins, downregulation of 26S proteasome subunits, and differential expression in proteins related to the ubiquitin-proteasome pathway lead to muscle atrophy. The differential expression might be due to the adaptative mechanism to counteract the deleterious effects of NaF on energy metabolism. Data are available via ProteomeXchange with identifier PXD035014.
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