Microcystin-LR promotes melanoma cell invasion and enhances matrix metalloproteinase-2/-9 expression mediated by NF-κB activation.

Abstract

This study aimed to explore the molecular mechanisms behind the stimulation effects of microcystin-LR (a well-known cyanobacterial toxin produced in eutrophic lakes or reservoirs) on cancer cell invasion and matrix metalloproteinases (MMPs) expression. Boyden chamber assay showed that microcystin-LR exposure (>12.5 nM) evidently enhanced the invasion ability of the melanoma cells (MDA-MB-435). Tumor Metastasis PCR Array demonstrated that 24 h microcystin-LR treatment (25 nM) caused overexpression of eight genes involved in tumor metastasis, including MMP-2, MMP-9, and MMP-13. Quantitative real-time PCR, Western blotting and gelatin zymography consistently demonstrated that mRNA and protein levels of MMP-2/-9 were increased in the cells after microcystin-LR exposure (P < 0.05 each). Immunofluorescence assay and electrophoretic mobility shift assay revealed that microcystin-LR could activate nuclear factor kappaB (NF-κB) by accelerating NF-κB translocation into the nucleus and enhancing NF-κB binding ability. Furthermore, addition of NF-κB inhibitor in culture medium could suppress the invasiveness enhancement and MMP-2/-9 overexpression. This study indicates that microcystin-LR can act as a NF-κB activator to promote MMP-2/-9 expression and melanoma cell invasion, which deserves more environmental health concerns.

• Authors: Xu-Xiang Zhang, Ziyi Fu, Zongyao Zhang, Chen Miao, Pengfei Xu, Ting Wang, Liuyan Yang, Shupei Cheng
• Journal: Environmental science & technology (Environ Sci Technol) Vol. 46 Issue 20 Pg. 11319-26 (Oct 16 2012) ISSN: 1520-5851 [Electronic] United States
• PMID: 22992115 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Marine Toxins
• Microcystins
• NF-kappa B
• RNA, Messenger
• Water Pollutants, Chemical
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9
• cyanoginosin LR

Topics

• Cell Line, Tumor
• Harmful Algal Bloom
• Humans
• Marine Toxins
• Matrix Metalloproteinase 2 (genetics, metabolism)
• Matrix Metalloproteinase 9 (genetics, metabolism)
• Melanoma (metabolism, pathology)
• Microcystins (toxicity)
• NF-kappa B (metabolism)
• RNA, Messenger (metabolism)
• Water Pollutants, Chemical (toxicity)