Triptolide downregulates human GD3 synthase (hST8Sia I) gene expression in SK-MEL-2 human melanoma cells.
10.3858/emm.2010.42.12.088
- Author:
Haw Young KWON
1
;
Seok Jo KIM
;
Cheorl Ho KIM
;
Sung Wook SON
;
Kyoung Sook KIM
;
Jai Heon LEE
;
Su Il DO
;
Young Choon LEE
Author Information
1. Department of Biotechnology, Brain Korea 21 Center for Silver-Bio Industrialization, Dong-A University, Busan 604-714, Korea. yclee@dau.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
alpha-N-acetylneuraminate alpha-2,8-sialyltransferase;
gene expression regulation;
melanoma;
NF-kappaB;
triptolide
- MeSH:
Cell Proliferation/drug effects;
Diterpenes/*pharmacology;
Down-Regulation;
Epoxy Compounds/pharmacology;
Genes, Reporter;
Humans;
NF-kappa B/metabolism;
Phenanthrenes/*pharmacology;
Promoter Regions, Genetic;
Sialyltransferases/*biosynthesis/genetics;
Tumor Cells, Cultured
- From:Experimental & Molecular Medicine
2010;42(12):849-855
- CountryRepublic of Korea
- Language:English
-
Abstract:
In this study, we have shown that gene expression of human GD3 synthase (hST8Sia I) is suppressed by triptolide (TPL) in human melanoma SK-MEL-2 cells. To elucidate the mechanism underlying the downregulation of hST8Sia I gene expression in TPL-treated SK-MEL-2 cells, we characterized the TPL-inducible promoter region within the hST8Sia I gene using luciferase constructs carrying 5'-deletions of the hST8Sia I promoter. Functional analysis of the 5'-flanking region of the hST8Sia I gene demonstrated that the -1146 to -646 region, which contains putative binding sites for transcription factors c-Ets-1, CREB, AP-1 and NF-kappaB, functions as the TPL-inducible promoter of hST8Sia I in SK-MEL-2 cells. Site-directed mutagenesis and ChIP analysis indicated that the NF-kappaB binding site at -731 to -722 is crucial for TPL-induced suppression of hST8Sia I in SK-MEL-2 cells. This suggests that TPL induces down-regulation of hST8Sia I gene expression through NF-kappaB activation in human melanoma cells.
