Novel silver glycinate conjugate with 3D polymeric intermolecular self-assembly architecture; an antiproliferative agent which induces apoptosis on human breast cancer cells.

Abstract

The new water soluble silver(I) complex of glycine (GlyH) with formula [Ag3(Gly)2NO3]n (AGGLY) was synthesized. The compound was characterized by melting point (m.p.), Fourier-transform infrared (FT-IR), Ultraviolet–visible (UV–vis) and Nuclear Magnetic Resonance (1H-,13C NMR) spectroscopic techniques and X-ray crystallography. The in vitro cytotoxic activity of AGGLY against human breast adenocarcinoma cell lines: MCF-7 (hormone depended (HD)) and MDA-MB-231 (hormone independent (HI)) was determined. For comparison other adenocarcinoma cells such as human cervical adenocarcinoma (HeLa) cells and lung adenocarcinoma cells (A549) were also screened. AGGLY inhibits both breast cancer cell lines stronger than cisplatin. On the contrary, AGGLY, exhibits lower toxicity against fetal lung fibroblast (MRC-5) cells than cisplatin. Its genotoxicity against MRC-5 cells was detected from the presence or absence of micronucleus using fluorescence microscopy, while the in vivo genotoxicity was evaluated using Allium cepa model. The MCF-7 cells morphology suggests apoptotic pathway for their death. The apoptotic pathway was confirmed by cell cycle arrest, Acridine Orange/Ethidium Bromide (AO/EB) Staining, and permeabilization of the mitochondrial membrane tests. The molecular mechanism of action was further studied by the binding affinity of AGGLY towards the calf thymus (CT) DNA.