Document Detail


Indomethacin inhibits cell growth of medullary thyroid carcinoma by reducing cell cycle progression into S phase.
MedLine Citation:
PMID:  18791128     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Indomethacin, a non-steroidal anti-inflammatory drug (NSAID), has been reported to inhibit the growth of medullary thyroid carcinoma (MTC) cells in vitro. However, the mechanism of inhibition of MTC cell growth by indomethacin and its potency have yet to be revealed. We examined the effect of indomethacin on three different MTC cell lines (TT cells, DRO 81-1 cells and HRO 85-1 cells) and two non-MTC cells. The mechanism of indomethacin action in MTC cells was investigated by analyzing intracellular prostaglandin level, apoptosis, and cell cycle in TT cells. Indomethacin inhibited cell growth of all three MTC cell lines but not normal thyroid cells or anaplastic thyroid carcinoma cells. Indomethacin at 10 microM or greater showed a dose response inhibition of cell growth. Indomethacin at 25 muM, a putative therapeutic serum indomethacin level, showed potency similar to 100 to 200 nM sunitinib, a receptor tyrosine kinase inhibitor. To examine whether prostaglandin depletion might determine the inhibition of MTC cell growth, we created different prostaglandin E2 (PGE2) levels in TT cells using three different NSAIDs. A profound PGE2 depletion by indomethacin-ester, a potent cyclooxygenase (COX) II inhibitor, showed the least inhibition of cell growth. Indomethacin did not increase apoptosis of TT cells. Indomethacin, but not naproxen or indomethacin-ester, reduced cell cycle progression into S phase; this was unrelated to the degree of PGE2 depletion. The expression of phosphorylated retinoblastoma (pRb) protein that shifts cells from G(1) to S phase was reduced after exposure to indomethacin. In conclusion, indomethacin has specific anti-tumor effect on MTC cells, probably by reducing cell cycle progression into S phase rather than by prostaglandin depletion. Since no drug therapy is currently available for MTC, indomethacin may be one of the therapeutic candidates.
Authors:
Chisato Tomoda; Farhad Moatamed; Faramarz Naeim; Jerome M Hershman; Masahiro Sugawara
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-09-12
Journal Detail:
Title:  Experimental biology and medicine (Maywood, N.J.)     Volume:  233     ISSN:  1535-3702     ISO Abbreviation:  Exp. Biol. Med. (Maywood)     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-10-29     Completed Date:  2009-01-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100973463     Medline TA:  Exp Biol Med (Maywood)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1433-40     Citation Subset:  IM    
Affiliation:
GLA VA Medical Center, Los Angeles, CA 90073, USA.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology
Apoptosis / drug effects
Calcitonin / genetics
Carcinoembryonic Antigen / genetics
Carcinoma, Medullary / pathology*
Cell Cycle / drug effects*
Cell Line
Cell Proliferation / drug effects*
Cyclooxygenase Inhibitors / pharmacology*
Dinoprostone / metabolism
Gene Expression / drug effects
Humans
Indoles / pharmacology
Indomethacin / pharmacology*
Phosphorylation
Pyrroles / pharmacology
Retinoblastoma Protein / metabolism
S Phase / drug effects
Thyroid Neoplasms / pathology*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Carcinoembryonic Antigen; 0/Cyclooxygenase Inhibitors; 0/Indoles; 0/Pyrroles; 0/Retinoblastoma Protein; 0/sunitinib; 363-24-6/Dinoprostone; 53-86-1/Indomethacin; 9007-12-9/Calcitonin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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