Journal Article

Silver nanoparticles inhibit the function of hypoxia-inducible factor-1 and target genes: insight into the cytotoxicity and antiangiogenesis

Yang, Tieshan, Liu, Qianqian, Liu, Binlei, Cao, Fei, Yao, Qian, Wang, Xiuhong

2016

Overview

Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that is activated upon exposure to hypoxic stress. It modulates a number of cellular responses including proliferation, apoptosis, angiogenesis, and metabolism by activating a panel of target genes in response to hypoxia. The HIF-1 level is often upregulated in the hypoxic microenvironment of solid tumors, which contributes to cancer treatment failure. Here we report that silver nanoparticles (AgNPs), which are widely used as an antimicrobial agent, are an effective inhibitor of HIF-1. AgNPs inhibited the activation of a HIF-dependent reporter construct after the cells were exposed to hypoxic conditions or treated with cobalt chloride, a hypoxia mimetic agent. The AgNPs also interfered with the accumulation of HIF-1α protein and the induction of the endogenous HIF target genes, VEGF-A and GLUT1. Since both HIF-1 and vascular endothelial growth factor-A play an important role in angiogenesis, AgNPs also inhibited angiogenesis in vitro. Our data reveal a new mechanism of how AgNPs act on cellular function, that is, they disrupt HIF signaling pathway. This finding provides a novel insight into how AgNPs can inhibit cancer cell growth and angiogenesis.

• Publisher: Taylor & Francis Ltd,Dove Press,Dove Medical Press
• Subject: Angiogenesis / Antimicrobial agents / Apoptosis / Apoptosis - drug effects / Blotting, Western / Cancer / Cell culture / Cell growth / Cell Proliferation - drug effects / Cytotoxicity / Glucose Transporter Type 1 - genetics / Glucose Transporter Type 1 - metabolism / Humans / Hypoxia / Hypoxia - drug therapy / hypoxia-inducible factor / Hypoxia-Inducible Factor 1, alpha Subunit - antagonists & inhibitors / Lymphoma / Medical prognosis / Metastasis / Nanoparticles / Nanoparticles - administration & dosage / Nanoparticles - chemistry / Nematodes / Neoplasms - blood supply / Neoplasms - drug therapy / Neoplasms - pathology / Neovascularization, Pathologic - prevention & control / Original Research / Oxidative stress / Penicillin / Real-Time Polymerase Chain Reaction / Reverse Transcriptase Polymerase Chain Reaction / RNA, Messenger - genetics / Signal Transduction - drug effects / Silver - chemistry / Silver nanoparticle (AgNPs) / silver nanoparticles (AgNPs) / Spectrum analysis / transcriptional activity / Tumor Cells, Cultured / Vascular endothelial growth factor / Vascular Endothelial Growth Factor A - genetics / Vascular Endothelial Growth Factor A - metabolism / vascular endothelial growth factor-A