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

Abstract

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.

• Authors: Tieshan Yang, Qian Yao, Fei Cao, Qianqian Liu, Binlei Liu, Xiu-Hong Wang
• Journal: International journal of nanomedicine (Int J Nanomedicine) 2016 Vol. 11 Pg. 6679-6692 ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 27994464 (Publication Type: Journal Article)

Chemical References

• Glucose Transporter Type 1
• Hypoxia-Inducible Factor 1, alpha Subunit
• RNA, Messenger
• SLC2A1 protein, human
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Silver

Topics

• Apoptosis (drug effects)
• Blotting, Western
• Cell Proliferation (drug effects)
• Glucose Transporter Type 1 (genetics, metabolism)
• Humans
• Hypoxia (drug therapy)
• Hypoxia-Inducible Factor 1, alpha Subunit (antagonists & inhibitors)
• Nanoparticles (administration & dosage, chemistry)
• Neoplasms (blood supply, drug therapy, pathology)
• Neovascularization, Pathologic (prevention & control)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (drug effects)
• Silver (chemistry)
• Tumor Cells, Cultured
• Vascular Endothelial Growth Factor A (genetics, metabolism)