Trichostatin A induces mesenchymal-like morphological change and gene expression but inhibits migration and colony formation in human cancer cells

Abstract

Abstract. Histone deacetylases (HDACs) are enzymes that catalyze the removal of acetyl from lysine residues in histones and other proteins, which results in gene transcriptional repression and subsequent changes in signaling events. HDACs inhibitors (HDACIs) have been used to reverse the aberrant epigenetic changes associated with cancer. However, the effects of HDACIs on epithelial-mesenchymal transition (EMT) in human cancer cells remain unclear. EMT is a fundamental process governing morphogenesis in multicellular organisms and promotes cancer invasion and metastasis. In this study, human cancer cells were treated with the HDACI trichostatin A (TSA). TSA was found to induce mesenchymal-like morphological changes in BGC-823 human gastric cancer and MCF-7 breast cancer cells, and increase the expression levels of the mesenchymal markers Vimentin and Twist. However, the expression levels of the epithelial cell marker E-cadherin were also increased in response to TSA treatment, while cell migration was reduced by TSA. Furthermore, TSA decreased cancer cell colony formation in BGC-823 and MCF-7 cells, and led to the deregulation of β-catenin, a critical signaling molecule involved in EMT. In conclusion, the results suggested that TSA exhibits dual functions in EMT induction and inhibition in human cancer cells, but the detailed mechanisms require further investigation.

HDAC inhibitors, trichostatin A and valproic acid, increase E‑cadherin and vimentin expression but inhibit migration and invasion of cholangiocarcinoma cells

“…Han et al (34) reported that TSA induced a mesenchymallike morphology and vimentin expression in human gastric and breast cancer cells. However, E-cadherin expression was also increased and the migratory activity was decreased (34).…”

“…Han et al (34) reported that TSA induced a mesenchymallike morphology and vimentin expression in human gastric and breast cancer cells. However, E-cadherin expression was also increased and the migratory activity was decreased (34). Deprivation of E-cadherin increased migration and invasion and potentiated the metastatic potential of vimentin (35).…”

Valproic acid (VPA) inhibits the epithelial–mesenchymal transition in prostate carcinoma via the dual suppression of SMAD4

“…Han and colleagues confirmed the migration-inhibitory effect of trichostatin A (TSA), another HDACi. However, this group found that TSA also simultaneously induced mesenchymal-like morphological changes and up-regulated the expression of mesenchymal markers and E-cadherin (Han et al 2014).…”

4‐Phenybutyric acid promotes gastric cancer cell migration via histone deacetylase inhibition‐mediated HER3/HER4 up‐regulation

“…For example, 4‐PBA inhibits the migration of metastatic prostate cancer cells (McAuley et al, ), but has no effect on the migration of colorectal cancer cells (Lv et al, ). Trichostatin A (TSA) suppresses the migration of BGC‐823 human gastric cancer and MCF‐7 breast cancer cells, though it also induces mesenchymal‐like morphological changes with E‐cadherin upregulation (Han et al, ). Meanwhile, valporic acid, sodium butyrate, SAHA, and TSA augment cell migration and metastasis through the induction of protein kinase C and matrix metalloproteinases in hepatoma, breast cancer, and lung cancer cells (Lin et al, ).…”