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Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Int+J+Mol+Sci 2017 ; 18 (3): ä Nephropedia Template TP
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Vanillin Suppresses Cell Motility by Inhibiting STAT3-Mediated HIF-1? mRNA Expression in Malignant Melanoma Cells #MMPMID28257048
Park EJ; Lee YM; Oh TI; Kim BM; Lim BO; Lim JH
Int J Mol Sci 2017[Mar]; 18 (3): ä PMID28257048show ga
Recent studies have shown that vanillin has anti-cancer, anti-mutagenic, and anti-metastatic activity; however, the precise molecular mechanism whereby vanillin inhibits metastasis and cancer progression is not fully elucidated. In this study, we examined whether vanillin has anti-cancer and anti-metastatic activities via inhibition of hypoxia-inducible factor-1? (HIF-1?) in A2058 and A375 human malignant melanoma cells. Immunoblotting and quantitative real time (RT)-PCR analysis revealed that vanillin down-regulates HIF-1? protein accumulation and the transcripts of HIF-1? target genes related to cancer metastasis including fibronectin 1 (FN1), lysyl oxidase-like 2 (LOXL2), and urokinase plasminogen activator receptor (uPAR). It was also found that vanillin significantly suppresses HIF-1? mRNA expression and de novo HIF-1? protein synthesis. To understand the suppressive mechanism of vanillin on HIF-1? expression, chromatin immunoprecipitation was performed. Consequently, it was found that vanillin causes inhibition of promoter occupancy by signal transducer and activator of transcription 3 (STAT3), but not nuclear factor-?B (NF-?B), on HIF1A. Furthermore, an in vitro migration assay revealed that the motility of melanoma cells stimulated by hypoxia was attenuated by vanillin treatment. In conclusion, we demonstrate that vanillin might be a potential anti-metastatic agent that suppresses metastatic gene expression and migration activity under hypoxia via the STAT3-HIF-1? signaling pathway.