Antiproliferative efficacy and mechanism of action of aggregation-resistant, polymorphous nanosilver functionalized with asparagus phytochemicals (Ar-AgNPs) in the breast adenocarcinoma MDA-MB-231 cells

Abstract

Collective functionalization of therapeutic phytochemicals on metal nanoparticles enhances their stability in circulation, target-specific delivery, and therapeutic outcome. Here, we report a facile, green synthesis of silver nanoparticles using the phytochemicals of Asparagus racemosus (Ar, shatavari), a medicinal herb with reported anticancer potential. The nanoparticles (Ar-AgNPs) were found to possess strong antiproliferative, anticlonogenic, anti-migratory, and cell-death-inducing effects against the breast cancer cell line, MDA-MB-231. The nanosilver, synthesized using a green synthesis approach, was polymorphous with a size distribution between 20 and 40 nm and aggregation-resistant (zeta potential,–26.4 mV). The functionalization of the particles with Ar phytochemicals was confirmed with liquid chromatography-mass spectroscopy (LC/MS). The particles inhibited MDA-MB-231 cell proliferation with an IC50 of 25 ± 2 µg/mL. Ar-AgNPs disrupted the structural integrity of tubulin and strongly retarded the assembly competence of the protein to form microtubules. Ar-AgNPs, however, did not show any phase-specific cell cycle arrest but showed an accumulation of dead-cell fragments as a sub-G1 population. They nevertheless killed the cells, as verified using annexin-PI-based flow cytometry. Taken together, our findings suggest the anticancer potential of Ar-AgNPs can be attributed, at least in part, to their ability to disrupt the structural and functional integrity of tubulin.