Document Detail


Synergistic anti-proliferative effects of vitamin D derivatives and 9-cis retinoic acid in SH-SY5Y human neuroblastoma cells.
MedLine Citation:
PMID:  11457659     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This study examines the effect of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], 24,25-dihydroxyvitamin D(3) [24,25(OH)(2)D(3)], two vitamin D analogues (KH 1060 and EB 1089, which are 20-epi-22-oxa and 22,24-diene-analogues, respectively), 9-cis retinoic acid and all-trans retinoic acid on proliferation of SH-SY5Y human neuroblastoma cells, after treatment for 7 days. Cell number did not change when the cells were incubated with 1, 10 or 100 nM 1,25(OH)(2)D(3) or its derivatives, but significantly decreased in the presence of the two retinoids (0.001--10 microM final concentration). A synergistic inhibition was observed, when SH-SY5Y cells were treated combining 0.1 microM 9-cis retinoic acid and 10 nM 1,25(OH)(2)D(3) or 10 nM KH 1060, and 1 microM 9-cis retinoic acid and 10 nM 1,25(OH)(2)D(3) or 10 nM EB 1089. Acetylcholinesterase activity showed a significant increase, in comparison with controls, after treatment of the cells for 7 days with 0.1 or 1 microM 9-cis retinoic acid, alone or combined with 10 nM 1,25(OH)(2)D(3) or 10 nM KH 1060 or 10 nM EB 1089. This increase was synergistic, combining 1 microM 9-cis retinoic acid and 10 nM 1,25(OH)(2)D(3) or EB 1089. The levels of the c-myc encoded protein remarkably decreased after treatment of SH-SY5Y cells for 1, 3, 7 days with 0.1 and 1 microM 9-cis retinoic acid, alone or combined with 10 nM 1,25(OH)(2)D(3) or 10 nM KH 1060 or 10 nM EB 1089. In particular, the association of 1 microM 9-cis retinoic acid and 10 nM 1,25(OH)(2)D(3) or 10 nM EB 1089 resulted in a synergistic c-myc inhibition, in comparison with that obtained in the presence of the retinoid alone. These findings may have therapeutic implications in human neuroblastoma.
Authors:
M Stio; A Celli; C Treves
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of steroid biochemistry and molecular biology     Volume:  77     ISSN:  0960-0760     ISO Abbreviation:  J. Steroid Biochem. Mol. Biol.     Publication Date:  2001 Jun 
Date Detail:
Created Date:  2001-07-17     Completed Date:  2001-08-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9015483     Medline TA:  J Steroid Biochem Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  213-22     Citation Subset:  IM    
Affiliation:
Department of Biochemical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy.
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MeSH Terms
Descriptor/Qualifier:
Acetylcholinesterase / drug effects,  metabolism
Antineoplastic Agents / pharmacology*
Cell Division / drug effects
Drug Synergism
Gene Expression / drug effects
Humans
Neuroblastoma / enzymology,  pathology*
Proto-Oncogene Proteins c-myc / drug effects,  genetics,  metabolism
Steroid Hydroxylases / pharmacology*
Tretinoin / pharmacology*
Tumor Cells, Cultured
Vitamin D / analogs & derivatives
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Proto-Oncogene Proteins c-myc; 1406-16-2/Vitamin D; 302-79-4/Tretinoin; 5300-03-8/alitretinoin; EC 1.14.-/Steroid Hydroxylases; EC 1.14.-/vitamin D 1-alpha hydroxylase; EC 3.1.1.7/Acetylcholinesterase

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