Journal
CANCER LETTERS
Volume 319, Issue 2, Pages 182-189Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2012.01.012
Keywords
Sphingosine 1-phosphate (S1P); Retinoids; All-trans retinoic acid (ATRA); HT-29 cells; Retinoid acid receptor beta (RAR beta); SphK2
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Funding
- Natural Science Foundation of China [81173090, 30973550, 81072665]
- Shandong Provincial Foundation for Natural Science [2009ZRB01798]
- Doctoral Science Foundation of the Ministry of Education of China [20090131110063]
- Department of Pathology and Laboratory Medicine, University of Calgary and Calgary Laboratory Services, Canada
- Dartmouth Medical School, USA
- Kobe University, Japan
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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. SIP antagonized ATRA activity on HT-29 cell proliferation and retinoic acid receptor beta (RAR beta) expression. SIP treatment or transient co-transfection with SphK2 expression vector antagonized ATRA-induced RAR beta promoter activity. Proteasome inhibition prevented SIP-induced modulation of ATRA activity. Overall, SIP antagonized ATRA's inhibitory effects by down-regulating RAR beta expression, likely via the proteasome-dependent pathway. Decreasing SIP production or inhibiting SphK2 activity could enhance the efficacy of retinoids in cancer treatments. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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