Insights on the interactions of human serum albumin with three natural phenylethanoid glycosides that inhibit HeLa cells proliferation

Abstract

Phenylethanol glycosides (PhGs) possessing various biological activities and good safety, are a large group of natural compounds extensively distributed in plant species. However, the interaction of PhGs with human serum albumin (HSA) is not reported, which is of guiding significance to expound the absorption and metabolism mechanism of PhGs in vivo. In this work, three natural PhGs containing biogenetic relationships, namely acteoside, cistanoside F, and decaffeoylacteoside were selected to investigate the cytotoxicity activity on human cervical cancer cell line (HeLa). Further, the binding affinity and mechanism of three PhGs with HSA were comprehensively elaborated by fluorescence spectroscopy, nuclear magnetic resonance, circular dichroism, atomic force microscopy and molecular docking. The results displayed that three PhGs inhibited the HeLa cells growth in a concentration-dependent manner with the IC50 values of 22.84, 78.20 and 47.86 μM, respectively. Fluorescence spectra demonstrated the fluorescence strength of HSA was obviously quenched by acteoside and cistanoside F, while amazingly the fluorescence strength of HSA was enhanced by decaffeoylacteoside. Spectroscopic technologies demonstrated three PhGs can be bound to HSA with the higher affinity (the binding constant Ka of PhGs 1, 2 and 3 was 1.23, 1.14 and 0.65 × 105, respectively) mainly through hydrophobic forces and hydrogen bonds, and the secondary configuration of HSA after treating with the PhGs was also mainly α-helix. Microscopic technology exhibited that HSA became more expanded and dispersed when combined with the PhGs. Molecular docking presented the molecular recognition pattern and evaluated the stability of the binary system between the PhGs and HSA.