Document Detail


Proteasome inhibitors induce apoptosis in growth hormone- and prolactin-secreting rat pituitary tumor cells.
MedLine Citation:
PMID:  12208657     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Proteasome inhibitors induce apoptosis in some malignant cells, and we show here that these inhibitors induce apoptosis in rat pituitary MMQ and GH3 tumor cells but not in normal pituitary cells. Three proteasome inhibitors, PSI, MG-132, and lactacystin, but not the calpain inhibitor, ALLM, dose- and time-dependently caused apoptosis in these cells, and 10 microM PSI caused apoptosis in 70% of MMQ cells and in 25% of GH3 cells within 24 h. A lower PSI dose (10 nM) inhibited GH3 cell growth without causing significant apoptosis or affecting prolactin secretion. Primary rat pituitary cells were resistant to both PSI and MG-132 and did not undergo apoptosis. In MMQ cells, DNA synthesis was slowed (approximately 30%) after 6 h of 10 microM PSI treatment and a partial cell cycle block at G2/M was evident after 8 h. Colorimetric caspase substrate assay and Western blotting of caspase substrates showed that caspases 2 and 3 are activated by PSI while caspases 6 and 8 remained inactive. A broad-range caspase inhibitor, caspase inhibitor III, prevented apoptosis induced by PSI. The results show that proteasome inhibitors induce apoptosis in rat pituitary tumor cells by specific caspase activation. This novel group of drugs may potentially be used in treatment of aggressive pituitary tumors, especially as their action appears relative for tumor cells.
Authors:
R Yu; S-G Ren; S Melmed
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of endocrinology     Volume:  174     ISSN:  0022-0795     ISO Abbreviation:  J. Endocrinol.     Publication Date:  2002 Sep 
Date Detail:
Created Date:  2002-09-04     Completed Date:  2002-11-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0375363     Medline TA:  J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  379-86     Citation Subset:  IM    
Affiliation:
Cedars-Sinai Research Institute, UCLA School of Medicine, 8700 Beverly Blvd, Los Angeles, CA 90048, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetylcysteine / analogs & derivatives*,  pharmacology
Animals
Apoptosis / drug effects*
Blotting, Western / methods
Caspases / metabolism
Cells, Cultured
Cysteine Endopeptidases
Enzyme Activation / drug effects
Enzyme Inhibitors / pharmacology*
Female
Growth Hormone / secretion
In Situ Nick-End Labeling
Leupeptins / pharmacology
Multienzyme Complexes / antagonists & inhibitors*
Pituitary Gland, Anterior / cytology,  drug effects
Pituitary Neoplasms / pathology*,  secretion
Prolactinoma / pathology
Proteasome Endopeptidase Complex
Rats
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
CA 75979/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Leupeptins; 0/Multienzyme Complexes; 133343-34-7/lactacystin; 133407-82-6/benzyloxycarbonylleucyl-leucyl-leucine aldehyde; 616-91-1/Acetylcysteine; 9002-72-6/Growth Hormone; EC 3.4.22.-/Caspases; EC 3.4.22.-/Cysteine Endopeptidases; EC 3.4.25.1/Proteasome Endopeptidase Complex

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


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