Spectroscopic study and in vitro anticancer effect toward colorectal cancer cells of a hydroxyaurone leptosidin...

This paper investigated the interaction between leptosidin, an aurone-based derivative and a subset of the flavone family, and transferrin using a variety of spectroscopic, molecular docking, and molecular dynamic investigations. The anticancer mechanism of leptosidin and transferrin-leptosidin complex against colorectal cancer cells was then assessed. It was demonstrated that the addition of leptosidin resulted in a significant quenching of transferrin's fluorescence intensity and a redshift of 8 nm. Moreover, a static transferrin-leptosidin complex with a single binding capability and logKa values ranging from 4.80 to 4.43 was generated, mostly by hydrogen bonding and electrostatic interactions. Fluctuations and disruptions in the transferrin structure and binding site properties were discovered through molecular docking, synchronous fluorescence spectroscopy, second derivative fluorescence spectroscopy, circular dichroism (CD), and molecular dynamic simulation studies after interaction with leptosidin. Cellular assays showed that complexing leptosidin with transferrin improved its anticancer effects in colorectal cancer cells. Better cellular internalization, membrane leakage, inhibition of colony formation, and upregulation of caspase-9 and -3 expression and activity in comparison with leptosidin were the mechanisms underlying the improved anticancer effect of complex species. Finally, it was demonstrated that the leptosidin-transferrin complex's antiproliferative actions were mediated by the downregulation of the PI3K/Akt signaling pathway in colorectal cancer cells. Further research is necessary to fully understand the evolution of anticancer drug-protein complexes, although this paper may provide insightful information in the interim.