Abstract
Even though phenazines have been extensively reported as anticancer molecules, the molecular target of these compounds is severely lagging behind. Our study consequently focuses on the anticancer target of a phenazine analogue (CPUL1) for its potently antitumor activities in initial stage. Along with redox status courses of Hep G2 cells, thioredoxin reductase I (TrxR1) was speculated as anticancer target of CPUL1. By virtue of zymologic, immunological and molecular biological experiments, we demonstrated that TrxR1 could be the anticancer target of CPUL1. The knowledge on phenazine targeting to TrxR1 have not been reported previously. Thus, it can provide valuable information for further development of the TrxR1 inhibitors.
Highlights
Thioredoxin reductases (TrxR, EC 1.8.1.9) are dimeric flavoproteins belonging to the family of pyridine nucleotide-disulphide oxidoreductases, which is found in different types of cancer cells cytoplasm
TrxR overexpression is essential to maintain the phenotypes of cancer cells, and emerging evidence has demonstrated the physiological and pathological significance of TrxR1 in cellular redox signalling networks, which are involved in virtually all aspects of cell functions, such as differentiation, proliferation and death[1]
With our ongoing study on the detailed antitumor molecular mechanism of compound CPUL1, we found that the compound was prevailingly distributed thoroughly in Hep G2 cell plasma not in cytoplast (Figure 1(B)), which was confirmed by laser scanning confocal microscopy (LSCM)
Summary
Thioredoxin reductases (TrxR, EC 1.8.1.9) are dimeric flavoproteins belonging to the family of pyridine nucleotide-disulphide oxidoreductases, which is found in different types of cancer cells cytoplasm. We tried to verify if there were significant differences between Trx1red/Trx1total and GSH/GSSG levels under treatment of CPUL1 in Hep G2 cell lines.
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