title: 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.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210046, China.
authors.forename: Xu-Xiang
authors.initials: XX
authors.lastname: Zhang
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Fu
authors.forename: Zongyao
authors.initials: Z
authors.lastname: Zhang
authors.forename: Chen
authors.initials: C
authors.lastname: Miao
authors.forename: Pengfei
authors.initials: P
authors.lastname: Xu
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.forename: Liuyan
authors.initials: L
authors.lastname: Yang
authors.forename: Shupei
authors.initials: S
authors.lastname: Cheng
mesh_terms: D045744:Cell Line, Tumor; D057097:Harmful Algal Bloom; D006801:Humans; D008387:Marine Toxins; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D052998:Microcystins / Q000633:toxicity*; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D008387:Marine Toxins; D052998:Microcystins; D016328:NF-kappa B; D012333:RNA, Messenger; D014874:Water Pollutants, Chemical; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C057862:cyanoginosin LR