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Sphingosine 1-phosphate antagonizes the effect of all-trans retinoic acid (ATRA) in a human colon cancer cell line by modulation of RARβ expression.

Abstract
All-trans retinoic acid (ATRA) is a promising therapeutic agent, but exhibits low efficacy against human cancers. We investigated the effect of sphingosine-1-phosphate (S1P) on ATRA activity in human colon cancer HT-29 cells. S1P antagonized ATRA activity on HT-29 cell proliferation and retinoic acid receptor beta (RARβ) expression. S1P treatment or transient co-transfection with SphK2 expression vector antagonized ATRA-induced RARβ promoter activity. Proteasome inhibition prevented S1P-induced modulation of ATRA activity. Overall, S1P antagonized ATRA's inhibitory effects by down-regulating RARβ expression, likely via the proteasome-dependent pathway. Decreasing S1P production or inhibiting SphK2 activity could enhance the efficacy of retinoids in cancer treatments.
AuthorsDe-Fu Sun, Zu-Hua Gao, Hui-Ping Liu, Yi Yuan, Xian-Jun Qu
JournalCancer letters (Cancer Lett) Vol. 319 Issue 2 Pg. 182-189 (Jun 28 2012) ISSN: 1872-7980 [Electronic] Ireland
PMID22261335 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012. Published by Elsevier Ireland Ltd.
Chemical References
  • Leupeptins
  • Lysophospholipids
  • Proteasome Inhibitors
  • Receptors, Retinoic Acid
  • retinoic acid receptor beta
  • sphingosine 1-phosphate
  • Tretinoin
  • Sphingosine
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde
Topics
  • Cell Proliferation (drug effects)
  • Colonic Neoplasms (genetics)
  • Down-Regulation
  • HT29 Cells
  • Humans
  • Leupeptins (pharmacology)
  • Lysophospholipids (pharmacology)
  • Proteasome Inhibitors
  • Receptors, Retinoic Acid (genetics, metabolism)
  • Sphingosine (analogs & derivatives, pharmacology)
  • Tretinoin (antagonists & inhibitors, pharmacology)

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