Freire Boullosa, Laurie;Van Loenhout, Jinthe;Flieswasser, Tal;De Waele, Jorrit;Hermans, Christophe;Lambrechts, Hilde;Cuypers, Bart;Laukens, Kris;Bartholomeus, Esther;Siozopoulou, Vasiliki;De Vos, Winnok H.;Peeters, Marc;Smits, Evelien L. J.;Deben, Christophe published 《Auranofin reveals therapeutic anticancer potential by triggering distinct molecular cell death mechanisms and innate immunity in mutant p53 non-small cell lung cancer》 in 2021. The article was appeared in 《Redox Biology》. They have made some progress in their research.Synthetic Route of C20H36AuO9PS The article mentions the following:
To shed light on the mode of action, this study provides an in-depth anal. on the mol. mechanisms and immunogenicity of AF-mediated cytotoxicity in the non-small cell lung cancer (NSCLC) cell line NCI-H1299 (p53 Null) and its two isogenic derivates with mutant p53 R175H or R273H accumulation. TrxR is highly expressed in a panel of 72 NSCLC patients, making it a valid druggable target in NSCLC for AF. The presence of mutant p53 overexpression was identified as an important sensitizer for AF in (isogenic) NSCLC cells as it was correlated with reduced thioredoxin (Trx) levels in vitro. Transcriptome anal. revealed dysregulation of genes involved in oxidative stress response, DNA damage, granzyme A (GZMA) signaling and ferroptosis. Although functionally AF appeared a potent inhibitor of GPX4 in all NCI-H1299 cell lines, the induction of lipid peroxidation and consequently ferroptosis was limited to the p53 R273H expressing cells. In the p53 R175H cells, AF mainly induced large-scale DNA damage and replication stress, leading to the induction of apoptotic cell death rather than ferroptosis. Importantly, all cell death types were immunogenic since the release of danger signals (ecto-calreticulin, ATP and HMGB1) and dendritic cell maturation occurred irresp. of (mutant) p53 expression. Finally, we show that AF sensitized cancer cells to caspase-independent natural killer cell-mediated killing by downregulation of several key targets of GZMA.((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold (cas: 34031-32-8) were involved in the experimental procedure.
((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold(cas: 34031-32-8) is a potent inhibitor of selenoenzyme thioredoxin reductase (TrxR), which is involved in defense against oxidative stress.Synthetic Route of C20H36AuO9PS
Reference:
Phosphine ligand,
Chiral phosphines in nucleophilic organocatalysis