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.
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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)
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Chemical References |
- Marine Toxins
- Microcystins
- NF-kappa B
- RNA, Messenger
- Water Pollutants, Chemical
- Matrix Metalloproteinase 2
- Matrix Metalloproteinase 9
- cyanoginosin LR
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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)
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