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.
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Authors | De-Fu Sun, Zu-Hua Gao, Hui-Ping Liu, Yi Yuan, Xian-Jun Qu |
Journal | Cancer letters
(Cancer Lett)
Vol. 319
Issue 2
Pg. 182-189
(Jun 28 2012)
ISSN: 1872-7980 [Electronic] Ireland |
PMID | 22261335
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 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
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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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