Abstract | BACKGROUND: METHODS: RESULTS: Treatment with TSA and VA resulted in decreased protein activity of MMP-2 and MMP-9 in all cell lines in a dose-dependent manner after 48 hours of treatment compared with untreated controls. In addition, 5-, TSA, and VA caused inhibition of growth in the range of 25-80% for all cell lines at 24, 48, and 72 hours. VA and TSA significantly decreased cell invasion in the FTC-133 and TPC-1 cell lines. CONCLUSION: The HDAC inhibitors TSA and VA decreased the protein activity of MMP-2 and MMP-9 and, in combination with the demethylating agent 5-AZC, inhibited cellular growth in human papillary and follicular thyroid cancer cell lines. These results elucidate our understanding of the pathways affected by the demethylating agents and HDAC inhibitors, and provide further evidence that MMPs are a potentially useful target for molecular therapies in patients with aggressive or refractory thyroid cancers.
|
Authors | Elliot J Mitmaker, Nicholas J Griff, Raymon H Grogan, Rajabrata Sarkar, Electron Kebebew, Quan-Yang Duh, Orlo H Clark, Wen T Shen |
Journal | Surgery
(Surgery)
Vol. 149
Issue 4
Pg. 504-11
(Apr 2011)
ISSN: 1532-7361 [Electronic] United States |
PMID | 21193210
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2011 Mosby, Inc. All rights reserved. |
Chemical References |
- Antimetabolites, Antineoplastic
- Histone Deacetylase Inhibitors
- Hydroxamic Acids
- Matrix Metalloproteinase Inhibitors
- trichostatin A
- Valproic Acid
- MMP2 protein, human
- Matrix Metalloproteinase 2
- Matrix Metalloproteinase 9
- Azacitidine
|
Topics |
- Adenocarcinoma, Follicular
(drug therapy, enzymology)
- Adenocarcinoma, Papillary
(drug therapy, enzymology)
- Antimetabolites, Antineoplastic
(therapeutic use)
- Azacitidine
(therapeutic use)
- Cell Line, Tumor
- Drug Screening Assays, Antitumor
- Histone Deacetylase Inhibitors
(pharmacology, therapeutic use)
- Humans
- Hydroxamic Acids
(therapeutic use)
- Matrix Metalloproteinase 2
(metabolism)
- Matrix Metalloproteinase 9
(metabolism)
- Matrix Metalloproteinase Inhibitors
- Thyroid Neoplasms
(drug therapy, enzymology)
- Valproic Acid
(therapeutic use)
|