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Int. J. Mol. Sci. 2017, 18(3), 532;

Vanillin Suppresses Cell Motility by Inhibiting STAT3-Mediated HIF-1α mRNA Expression in Malignant Melanoma Cells

Department of Biomedical Chemistry, College of Biomedical & Health Science, Konkuk University, Chungju 380-701, Korea
Interdisciplinary Research Center for Health, Konkuk University, Chungju 380-701, Korea
Severance Integrative Research Institute for Cerebral and Cardiovascular Diseases (SIRIC), Yonsei University College of Medicine, Seodamun-gu, Seoul 03722, Korea
Author to whom correspondence should be addressed.
Academic Editor: Toshio Morikawa
Received: 6 January 2017 / Revised: 23 February 2017 / Accepted: 24 February 2017 / Published: 1 March 2017
(This article belongs to the Special Issue Biological Activity of Natural Secondary Metabolite Products)
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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-1α (HIF-1α) in A2058 and A375 human malignant melanoma cells. Immunoblotting and quantitative real time (RT)-PCR analysis revealed that vanillin down-regulates HIF-1α protein accumulation and the transcripts of HIF-1α 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-1α mRNA expression and de novo HIF-1α protein synthesis. To understand the suppressive mechanism of vanillin on HIF-1α 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-κB (NF-κB), 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-1α signaling pathway. View Full-Text
Keywords: vanillin; HIF-1α; STAT3; migration; melanoma vanillin; HIF-1α; STAT3; migration; melanoma

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Park, E.-J.; Lee, Y.-M.; Oh, T.-I.; Kim, B.M.; Lim, B.-O.; Lim, J.-H. Vanillin Suppresses Cell Motility by Inhibiting STAT3-Mediated HIF-1α mRNA Expression in Malignant Melanoma Cells. Int. J. Mol. Sci. 2017, 18, 532.

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