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

Authors
 Eun-Ji Park  ;  Yoon-Mi Lee  ;  Taek-In Oh  ;  Byeong Mo Kim  ;  Beong-Ou Lim  ;  Ji-Hong Lim 
Citation
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.18(3) : E532, 2017 
Journal Title
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN
 1661-6596 
Issue Date
2017
MeSH
Benzaldehydes/pharmacology* ; Cell Line, Tumor ; Cell Movement/drug effects* ; Gene Expression Regulation, Neoplastic/drug effects* ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Melanoma/genetics* ; Melanoma/metabolism* ; Promoter Regions, Genetic ; Protein Binding ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; STAT3 Transcription Factor/metabolism* ; Transcriptional Activation
Keywords
HIF-1α ; STAT3 ; melanoma ; migration ; vanillin
Abstract
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
Files in This Item:
T201700472.pdf Download
DOI
10.3390/ijms18030532
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
Yonsei Authors
Kim, Byeong Mo(김병모) ORCID logo https://orcid.org/0000-0002-0582-3132
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/166582
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