Upregulation of Human ST8Sia VI (α2,8-Sialyltransferase) Gene Expression by Physcion in SK-N-BE(2)-C Human Neuroblastoma Cells

Int J Mol Sci. 2016 Aug 2;17(8):1246. doi: 10.3390/ijms17081246.


In this research, we firstly demonstrated that physcion, an anthraquinone derivative, specifically increased the expression of the human α2,8-sialyltransferase (hST8Sia VI) gene in SK-N-BE(2)-C human neuroblastoma cells. To establish the mechanism responsible for the up-regulation of hST8Sia VI gene expression in physcion-treated SK-N-BE(2)-C cells, the putative promoter region of the hST8Sia VI gene was functionally characterized. Promoter analysis with serially truncated fragments of the 5'-flanking region showed that the region between -320 and -240 is crucial for physcion-induced transcription of hST8Sia VI in SK-N-BE(2)-C cells. Putative binding sites for transcription factors Pax-5 and NF-Y are located at this region. The Pax-5 binding site at -262 to -256 was essential for the expression of the hST8Sia VI gene by physcion in SK-N-BE(2)-C cells. Moreover, the transcription of hST8Sia VI induced by physcion in SK-N-BE(2)-C cells was inhibited by extracellular signal-regulated protein kinase (ERK) inhibitor U0126 and p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580, but not c-Jun N-terminal kinase (JNK) inhibitor SP600125. These results suggest that physcion upregulates hST8Sia VI gene expression via ERK and p38 MAPK pathways in SK-N-BE(2)-C cells.

Keywords: SK-N-BE(2)-C; hST8Sia VI; physcion; signal pathway; transcription factor Pax-5.

MeSH terms

  • 5' Flanking Region / genetics
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Base Sequence
  • Brain Neoplasms / enzymology
  • Brain Neoplasms / genetics*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Emodin / analogs & derivatives*
  • Emodin / chemistry
  • Emodin / isolation & purification
  • Emodin / pharmacology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Neuroblastoma / enzymology
  • Neuroblastoma / genetics*
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sequence Analysis, DNA
  • Sequence Deletion
  • Sialyltransferases / genetics*
  • Sialyltransferases / metabolism
  • Transcriptional Activation / drug effects
  • Transcriptional Activation / genetics
  • Up-Regulation / drug effects*
  • Up-Regulation / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • RNA, Messenger
  • Sialyltransferases
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases
  • ST8SIA6 protein, human
  • physcione
  • Emodin