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

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/486839.do
DOI
10.3390/ijms18030532
Title
Vanillin Suppresses Cell Motility by Inhibiting STAT3-Mediated HIF-1alpha mRNA Expression in Malignant Melanoma Cells
Description
This study was supported by the National Research Foundation of Korea(NRF) grant funded by the Korean Government (2014R1A2A2A04007791 and2015R1A2A2A01002483).
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-1 alpha (HIF-1 alpha) in A2058 and A375 human malignant melanoma cells. Immunoblotting and quantitative real time (RT)-PCR analysis revealed that vanillin down-regulates HIF-1 alpha protein accumulation and the transcripts of HIF-1 alpha 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 alpha mRNA expression and de novo HIF-1 alpha protein synthesis. To understand the suppressive mechanism of vanillin on HIF-1 alpha 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-kappa B (NF-kappa 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 alpha signaling pathway.
provenance
Made available in Cube on 2018-09-28T16:18:17Z (GMT). No. of bitstreams: 0
language
English
author
Park, Eun-Ji
Lee, Yoon-Mi
Oh, Taek-In
Kim, Byeong Mo
Lim, Beong-Ou
Lim, Ji-Hong
accessioned
2018-09-28T16:18:17Z
available
2018-09-28T16:18:17Z
issued
2017
citation
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES(18): 3
issn
1422-0067
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/486839.do
Funder
미래창조과학부
Funding Program
개인연구지원
Project ID
1711037515
Jurisdiction
Rep.of Korea
Project Name
Elucidation of differential roles of SIRT1-HIF-2α regulatory axis in neural injury and development of small molecules targeting SIRT1-HIF-2α axis
rights
openAccess
subject
vanillin
HIF-1 alpha
STAT3
migration
melanoma
type
article


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