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

Kim, Sung Ok; Choi, Byung Tae; Choi, Ik Jun; Cheong, Jae Hun; Kim, Jin Chul; Kwon, Taeg Kyu; Kim, Nam Deuk; Choi, Yung Hyun

doi:10.5483/bmbrep.2009.42.10.655

Cited by 22 publications

(12 citation statements)

References 15 publications

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“…IGF-1R is frequently overexpressed in several cancers and the tumor-genetic salivary gland epithelial cells model and is now an attractive anticancer treatment target (42,43). Previous studies have shown that HDAC inhibitors inhibited IGF-1R expression in cancer cells (44,45). The present data also show that apicidin markedly inhibited the level of IGF-1R expression in YD-15 cells.…”

Section: Discussionsupporting

confidence: 74%

Apicidin inhibits cell growth by downregulating IGF-1R in salivary mucoepidermoid carcinoma cells

Ahn

Kim

et al. 2015

Oncology Reports

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Abstract. Inhibition of histone deacetylases (HDACs) has emerged as a new target for cancer therapies. The present study examined the antitumor effect and molecular mechanism of the HDAC inhibitor apicidin in YD-15 human salivary mucoepidermoid carcinoma (MEC) cells. The cells were treated with apicidin and cell death was quantified using an MTT assay. Apoptosis and autophagy were measured using flow cytometry, immunoblot analysis and cell staining. Regulation of the signaling pathways was monitored using immunoblot analysis and co-treatment with specific inhibitors. Insulin-like growth factor 1 receptor (IGF-1R) was knocked down using specific siRNA. Apicidin significantly inhibited the proliferation of MEC cells. Apicidin also induced apoptosis through the inactivation of extracellular signal-regulated kinase (ERK) and AKT/mTOR signaling and activation of c-Jun NH2-terminal kinase (JNK), whereas apicidin promoted autophagy through inactivation of the AKT/mTOR signaling. These effects may be mediated by the inhibition of IGF-1R, an upstream regulator of MAPK and AKT/mTOR pathways. These results suggested that apicidin is an attractive chemotherapeutic agent against salivary MEC and may be a good candidate for targeting IGF-1R for cancer therapies.

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Section: Discussionsupporting

confidence: 74%

Apicidin inhibits cell growth by downregulating IGF-1R in salivary mucoepidermoid carcinoma cells

Ahn

Kim

et al. 2015

Oncology Reports

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“…permeability (18,21,(23)(24)(25)(26). In the present study, we examined changes of TER values in order to investigate the relationship between anti-invasive activity and TJs in response to HAD-B treatment.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of cell motility and invasion by HangAmDan-B in NCI-H460 human non-small cell lung cancer cells

et al. 2011

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Abstract.Correlation between inhibition of cell motility and anti-invasive activity by the water extract of HangAmDan-B (HAD-B), a crude extract of eight Korean medicinal animals and plants, in NCI-H460 human non-small cell lung cancer (NSCLC) cells was investigated. Within the concentrations that were not cytotoxic, HAD-B induced significant concentrationdependent inhibition of cell motility and invasiveness of NCI-H460 cells. Treatment with HAD-B resulted in dosedependent inhibition of the activities of matrix metallo proteinase (MMP)-2 and MMP-9, and this was correlated with a decrease in expression of their mRNA and proteins, and upregulation of tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 expression. Anti-invasive activity of HAD-B was also found to be associated with increased tightness of the tight junction (TJ), as demonstrated by an increase in transepithelial electrical resistance. In addition, the present results indicated that treatment with HAD-B resulted in repression of the levels of claudin family members, which are major components of TJs that play a key role in control and selectivity of para cellular transport. Although further studies are needed, findings from the present study indicate that TJs and MMPs are critical targets of HAD-B-induced anti-invasiveness in NCI-H460 NSCLC cells.

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“…HDACis may be effective in reducing the metastatic potential of primary tumors. The potential antimetastasis and anti-invasion activities of Egr-1 and claudin-3, a tight-junction-related protein, were evaluated using HDACis in human hepato carcinoma cells [131]. HDACis upregulate metastasis suppressor genes, such as Kangai (KAII), Ras homologue genes, RhoB, RECK and TIMP-1.…”

Section: Hdac Inhibitor Capping Groupmentioning

confidence: 99%

Histone Deacetylase Inhibitors In The Treatment Of Cancer: Overview And Perspectives

et al. 2012

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Histone deacetylase inhibitors (HDACis) are one of the last frontiers in pharmaceutical research. Several classes of HDACi have been identified. Although more than 20 HDACi are under preclinical and clinical investigation as single agents and in combination therapies against different cancers, just two of them were approved by the US FDA: Zolinza(®) and Istodax(®), both licensed for the treatment of cutaneous T-cell lymphoma, the latter also of peripheral T-cell lymphoma. Since HDAC enzymes act by forming multiprotein complexes (clusters), containing cofactors, the main problem in designing new HDACi is that the inhibition activity evaluated on isolated enzyme isoforms does not match the in vivo outcomes. In the coming years, the research will be oriented toward a better understanding of the functioning of these protein complexes as well as the development of new screening assays, with the final goal to obtain new drug candidates for the treatment of cancer.

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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

Abstract: 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

Cited by 22 publications

References 15 publications

Apicidin inhibits cell growth by downregulating IGF-1R in salivary mucoepidermoid carcinoma cells

Apicidin inhibits cell growth by downregulating IGF-1R in salivary mucoepidermoid carcinoma cells

Inhibition of cell motility and invasion by HangAmDan-B in NCI-H460 human non-small cell lung cancer cells

Histone Deacetylase Inhibitors In The Treatment Of Cancer: Overview And Perspectives

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