Investigation of binary and ternary systems of human serum albumin with oxyresveratrol/piceatannol and/or mitoxantrone by multipectroscopy, molecular docking and cytotoxicity evaluation.

The combined application of polyphenols and anticancer drugs may be of great help to current cancer treatment. In this paper, the individual and combined interactions of oxyresveratrol (OXY)/piceatannol (PIC) and mitoxantrone (MIT) with human serum albumin (HSA) in phosphate buffer of pH 7.4 were studied by multi-spectroscopic techniques and molecular docking. The quenching mechanism of HSA by OXY, PIC and MIT was determined by fluorescence quenching experiments and UV difference spectra. The binding location of the three ligands on HSA was identified by site marking fluorescence spectra, synchronous fluorescence spectra, and molecular docking. For the OXY/PIC/MIT + HSA binary system and the OXY/PIC + MIT + HSA ternary system, the thermodynamic parameters were obtained. The results indicated the competitive binding of OXY/PIC and MIT to HSA. The driving forces in the binding process were discussed. The circular dichroism spectroscopy and dynamic light scattering were employed to investigate the effects of OXY/PIC/MIT single drug and OXY/PIC + MIT combined drugs on the secondary structure and particle size of HSA. The effects of drug combination and HSA interaction on the in vitro cytotoxicity against HeLa cells were determined by MTT assay. The results would provide a theoretical basis for the combined application of polyphenols and traditional anticancer drugs. Unlabelled Image • The quenching mechanism of HSA by OXY, PIC or MIT was static quenching. • The binding affinity with HSA decreased in the order of OXY > PIC>MIT. • OXY/PIC and MIT mainly competitively bound to subdomain IIA of HSA. • Drug-protein binding affected the secondary structure and particle size of HSA. • Drug combination and HSA complex demonstrated enhanced cytotoxicity. [ABSTRACT FROM AUTHOR]