PMID- 12956933
OWN - NLM
STAT- MEDLINE
DCOM- 20040210
LR  - 20121115
IS  - 1671-4083 (Print)
IS  - 1671-4083 (Linking)
VI  - 24
IP  - 9
DP  - 2003 Sep
TI  - Analysis of triptolide-regulated gene expression in Jurkat cells by complementary 
      DNA microarray.
PG  - 864-72
AB  - AIM: To investigate the global gene expression profile changes in Jurkat cells 
      after triptolide treatment in order to find the possible triptolide targets. 
      METHODS: Jurkat cells were treated with or without triptolide 10 microg/L for 2 
      h. Total RNA were isolated and used as templates for reverse transcriptional 
      labeling of fluorescent cDNA probes. High density DNA microarray chips with a set 
      of 13,872 human genes/Ests were used to generate the expression profile of 
      triptolide-treated or untreated control Jurkat cells by hybridizing with 
      fluorescent labeled probes. Array image was acquired and analyzed with array 
      analyzing software GeneSpring. RESULTS: Triptolide significantly suppressed 
      expression of 117 genes in Jurkat cells. Among these 117 genes, 30 % were Ests or 
      genes without known functions, 13 % were transcription factors, 9 % were signal 
      transduction pathway regulators, and 9 % were DNA binding proteins. Notably, the 
      expression of mitogen-activated protein kinase kinase kinase kinase 5 (MAP kinase 
      5) and phosphoinositide-3-kinase (PI-3 kinase) was inhibited more than 100-fold. 
      Moreover, the expression of genes involved in lipid transportation and metabolism 
      was down-regulated by triptolide. CONCLUSION: High-density microarray provided an 
      effective approach to identify drug targeting molecules. It is suggested that the 
      widely known immune suppressive and antitumor effects of triptolide were mediated 
      at least in part by suppression of MAP kinase and PI-3 kinase gene expression.
FAU - Du, Ze-Ying
AU  - Du ZY
AD  - Department of Pharmacology, Shanghai Institute of Materia Medica, Shanghai 
      Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, 
      China.
FAU - Li, Xiao-Yu
AU  - Li XY
FAU - Li, Yuan-Chao
AU  - Li YC
FAU - Wang, Shun-You
AU  - Wang SY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Acta Pharmacol Sin
JT  - Acta pharmacologica Sinica
JID - 100956087
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Diterpenes)
RN  - 0 (Epoxy Compounds)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Phenanthrenes)
RN  - 0 (RNA, Messenger)
RN  - 19ALD1S53J (triptolide)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 5)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinases)
RN  - EC 2.7.11.25 (MAP3K5 protein, human)
SB  - IM
MH  - Antineoplastic Agents, Phytogenic/*pharmacology
MH  - Diterpenes/isolation & purification/*pharmacology
MH  - Epoxy Compounds
MH  - Gene Expression Regulation/*drug effects
MH  - Humans
MH  - Immunosuppressive Agents/pharmacology
MH  - Jurkat Cells
MH  - MAP Kinase Kinase Kinase 5
MH  - MAP Kinase Kinase Kinases/*biosynthesis/genetics
MH  - Oligonucleotide Array Sequence Analysis
MH  - Phenanthrenes/isolation & purification/*pharmacology
MH  - Phosphatidylinositol 3-Kinases/*biosynthesis/genetics
MH  - Plants, Medicinal/chemistry
MH  - RNA, Messenger/genetics
MH  - Tripterygium/chemistry
EDAT- 2003/09/06 05:00
MHDA- 2004/02/11 05:00
CRDT- 2003/09/06 05:00
PHST- 2003/09/06 05:00 [pubmed]
PHST- 2004/02/11 05:00 [medline]
PHST- 2003/09/06 05:00 [entrez]
PST - ppublish
SO  - Acta Pharmacol Sin. 2003 Sep;24(9):864-72.