Triphala polyphenols-functionalized gold nanoparticles impair cancer cell survival through induction of tubulin dysfunction

Abstract

Green-nanotechnology has enabled the development of several potential nanomedicines against diseases such as cancer. Triphala is an ayurvedic formulation with anticancer activities. The aim of the study was to synthesize, characterize, and biologically evaluate Trl-polyphenol-coated gold nanoparticles (Trl-GNPs) and to elucidate the mechanism of action of this formulation. Trl-GNPs were synthesized using the lyophilized powder of Trl extract and gold chloride trihydrate, and characterized by an assortment of spectroscopy techniques (UV–visible spectroscopy, energy-dispersive X-ray spectroscopy, Fourier-transform infrared spectroscopy, size- and zeta potential-analysis, and one-dimensional proton nuclear magnetic resonance spectroscopy) and transmission electron microscopy. Cell viability analyses of the triple-negative breast cancer cell line, MDA-MB-231, were carried out using (3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay. The nature of interactions of the Trl-GNPs with the purified tubulin was studied using spectrofluorimetry and circular dichroism. Microtubule architectural defects were investigated using immunofluorescence microscopy. Trl-GNPs were found to be inhibitory to the proliferative potential of the cells. The antiproliferative mechanism of action of Trl-GNPs involved perturbation of the structural the integrity of the mitotic-spindle-building protein, tubulin, at the secondary and tertiary levels. These disruptions of tubulin manifested as disrupted microtubule network in cells facilitating cell cycle arrest. Our data suggest a potential method for enhancing the delivery of Trl polyphenols to cancer cells, and elucidate the antiproliferative mechanism of action of these particles.