PMID- 16475687
OWN - NLM
STAT- MEDLINE
DCOM- 20060309
LR  - 20151119
IS  - 0250-7005 (Print)
IS  - 0250-7005 (Linking)
VI  - 26
IP  - 1A
DP  - 2006 Jan-Feb
TI  - Sphinganine causes early activation of JNK and p38 MAPK and inhibition of AKT 
      activation in HT-29 human colon cancer cells.
PG  - 121-7
AB  - The sphingoid base sphinganine induces apoptosis in HT-29 human colon cancer 
      cells more potently than other bioactive sphingolipid metabolites sphingosine and 
      C2-ceramide tested in our previous study. The objective of this study was to 
      investigate the effect of sphinganine, at a concentration that induces apoptosis, 
      on the mitogen activated protein kinases (MAPKs) including ERK1/ERK2, JNK2/JNK1, 
      and p38 MAPK and AKT (protein kinase B), which regulate cell proliferation and 
      apoptosis. HT-29 cells were cultured with sphinganine at 35 microM and the 
      protein expression and phosphorylation status of ERK1/ERK2 (p44/p42), JNK2/JNK1 
      (p54/p46), p38 MAPK, and AKT were determined using Western blot analysis. 
      Sphinganine clearly increased the active phosphorylated forms of JNK2/JNK1 and 
      p38 MAPK after 15, 30, and 60 min treatment, with minimal effects on activation 
      of ERK1/ERK2. Sphinganine weakly inhibited the phosphorylation of AKT at ser473 
      after 30 and 60 min. Sphinganine had little or no effect on the protein 
      expression level of any of the kinases. The findings are consistent with a 
      mechanism by which sphinganine induces apoptosis in HT-29 cells via early and 
      strong activation of JNK and p38 MAPK and weak inhibition of AKT activation.
FAU - Ahn, Eun Hyun
AU  - Ahn EH
AD  - Department of Food Science and Human Nutrition, Michigan State University, East 
      Lansing, MI 48824-1224, USA. ahne@mail.med.upenn.edu
FAU - Schroeder, Joseph J
AU  - Schroeder JJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - EC 2.7.1.24 (Mitogen-Activated Protein Kinase 9)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 8)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - NGZ37HRE42 (Sphingosine)
RN  - OWA98U788S (safingol)
SB  - IM
MH  - Colonic Neoplasms/*drug therapy/*enzymology
MH  - Enzyme Activation
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - HT29 Cells
MH  - Humans
MH  - Mitogen-Activated Protein Kinase 8/*metabolism
MH  - Mitogen-Activated Protein Kinase 9/*metabolism
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/*antagonists & inhibitors/metabolism
MH  - Sphingosine/*analogs & derivatives/pharmacology
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
EDAT- 2006/02/16 09:00
MHDA- 2006/03/10 09:00
CRDT- 2006/02/16 09:00
PHST- 2006/02/16 09:00 [pubmed]
PHST- 2006/03/10 09:00 [medline]
PHST- 2006/02/16 09:00 [entrez]
PST - ppublish
SO  - Anticancer Res. 2006 Jan-Feb;26(1A):121-7.