Anti-invasive activity of histone deacetylase inhibitors via the induction of Egr-1 and the modulation of tight junction-related proteins in human hepatocarcinoma cells.
The potential anti-metastasis and anti-invasion activities of early growth response gene-1 (Egr-1) and claudin-3, a tight junction (TJ)-related protein, were evaluated using histone deacetylase (HDAC) inhibitors in human hepatocarcinoma cells. The results of wound healing and Transwell assays showed that HDAC inhibitors such as trichostatin A and sodium butyrate inhibited cell migration and invasion. HDAC inhibitors markedly induced Egr-1 expression during the early period, after which expression levels decreased. In addition, the down-regulation of snail and type 1 insulin-like growth factor receptor (IGF-1R) in HDAC inhibitor-treated cells induced the upregulation of thrombospondin-1 (TSP-1), E-cadherin and claudin-3. Cells transfected with Egr-1 and claudin-3 siRNA displayed significant blockage of HDAC inhibitor-induced anti-invasive activity. Collectively, these findings indicate that the up-regulation of Egr-1 and claudin-3 are crucial steps in HDAC inhibitor-induced anti-metastasis and anti-invasion.
Kim
Sung Ok
SO
Department of Biomaterial Control (BK21 Program), Dongeui University Graduate School, Busan 614-052, Korea.
Choi
Byung Tae
BT
Choi
Il-Whan
IW
Cheong
Jaehun
J
Kim
Gi-Young
GY
Kwon
Taeg Kyu
TK
Kim
Nam Deuk
ND
Choi
Yung Hyun
YH
D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D062465:Claudin-3; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D056945:Hep G2 Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism*
C568122:CLDN3 protein, human; D062465:Claudin-3; D051766:Early Growth Response Protein 1; D056572:Histone Deacetylase Inhibitors; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering