Document Detail

Follicular thyroid cancer cell growth inhibition by proteosome inhibitor MG132.
MedLine Citation:
PMID:  19552924     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Effective therapies for the subset of follicular thyroid cancer (FTC) patients with aggressive, metastatic disease are lacking. Therefore, we sought to determine the effects of proteosome inhibition, an emerging class of chemotherapeutic agents, on metastatic FTC cells.
MATERIALS AND METHODS: Human metastatic FTC cells (FTC236) were treated in vitro with the proteosome inhibitor MG132 (0 to 800 nM). Western blot analysis was performed on whole cell lysates isolated after 2 d. To measure cell growth, we performed an MTT cellular proliferation assay over 6 d.
RESULTS: Treatment of FTC236 cells with MG132 led to dose-dependent cell growth inhibition. Increases in inactive, phosphorylated GSK-3beta, and active beta-catenin also were observed. With 800 nM MG132, growth was reduced by 87% at 6 d (P < 0.0001). This reduction in cellular proliferation correlated with the degree of GSK-3beta inhibition. MG132 treatment also caused increased p21(Waf1/Cip1) and decreased cyclin D1 expression, suggesting that growth suppression may occur through cell cycle arrest.
CONCLUSION: Growth of metastatic human FTC cells appears to be suppressed by proteosome inhibition. Whether this effect is directly due to cell cycle arrest and inactivation of GSK-3beta signaling is unclear. Nonetheless, these compounds may become novel treatments for aggressive, metastatic FTC.
Samantha J Stoll; Susan C Pitt; Herbert Chen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-05-03
Journal Detail:
Title:  The Journal of surgical research     Volume:  156     ISSN:  1095-8673     ISO Abbreviation:  J. Surg. Res.     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-08-21     Completed Date:  2009-09-11     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  0376340     Medline TA:  J Surg Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  39-44     Citation Subset:  IM    
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MeSH Terms
Adenocarcinoma, Follicular / drug therapy*,  metabolism
Antineoplastic Agents / pharmacology,  therapeutic use*
Cell Cycle / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects*
Cyclin D1 / metabolism
Glycogen Synthase Kinase 3 / metabolism
Leupeptins / pharmacology,  therapeutic use*
Proteasome Inhibitors
Thyroid Neoplasms / drug therapy*,  metabolism
beta Catenin / metabolism
p21-Activated Kinases / metabolism
Grant Support
R01 CA109053/CA/NCI NIH HHS; R01 CA109053/CA/NCI NIH HHS; R01 CA109053-01A2/CA/NCI NIH HHS; R01 CA109053-02/CA/NCI NIH HHS; R01 CA109053-03/CA/NCI NIH HHS; R21 CA117117/CA/NCI NIH HHS; R21 CA117117/CA/NCI NIH HHS; R21 CA117117-01A2/CA/NCI NIH HHS; T32 CA009614/CA/NCI NIH HHS; T35 DK062709/DK/NIDDK NIH HHS; T35 DK062709-03/DK/NIDDK NIH HHS; T35 DK062709-03/DK/NIDDK NIH HHS; T35 DK062709-04/DK/NIDDK NIH HHS
Reg. No./Substance:
0/Antineoplastic Agents; 0/Leupeptins; 0/Proteasome Inhibitors; 0/beta Catenin; 133407-82-6/benzyloxycarbonylleucyl-leucyl-leucine aldehyde; 136601-57-5/Cyclin D1; EC synthase kinase 3 beta; EC Kinases; EC Synthase Kinase 3

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

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