Mehrnaz Jahani1, Hossein Khanahmad1, Parvaneh Nikpour2,3. 1. Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, 81746-73461, Iran. 2. Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, 81746-73461, Iran. pnikpour@med.mui.ac.ir. 3. Child Growth and Development Research Center, Research Institute for Primordial Prevention of Noncommunicable Disease, Isfahan, Iran. pnikpour@med.mui.ac.ir.
Abstract
PURPOSE: Metastasis is the most important feature of gastric cancer accounting for more than 90% of tumor-related mortality. As one of the main modulators of epithelial-mesenchymal transition (EMT), histone deacetylase inhibitors (HDACI) are considered rational candidates for cancer therapy. Valproic acid (VPA) is a HDACI with reported controversial effects on the EMT. The main aim of the current study was to evaluate the effects of VPA treatment on cell survival and EMT-related features of human gastric cancer cells (AGS). METHODS: Methyl-thiazoltetrazolium (MTT) assay was utilized to assess the effect of VPA on the proliferation rate of cells. Apoptotic cell death was detected with Annexin V/PI staining. Migratory ability of cells following VPA treatment was assessed using a Boyden chamber test. The expression of EMT markers in AGS cells was analyzed using quantitative real-time RT-PCR. RESULTS: Treatment with VPA significantly inhibited AGS cell proliferation compared with control. An increased rate of early and late apoptotic cells was observed following VPA exposure. It was demonstrated that VPA significantly diminished the cell migratory ability in AGS gastric cancer cells. Furthermore, treatment with VPA significantly decreased the expression of E-cadherin but increased the Vimentin expression. CONCLUSIONS: Our results showed that VPA induces apoptosis and inhibits the cell proliferation and the migratory ability of AGS gastric cancer cells and may prove useful in the development of therapeutic agents for human gastric cancer. However, these preliminary findings call for further investigations to clarify the precise molecular mechanisms by which VPA modulates the EMT process in a cell type-specific manner.
PURPOSE: Metastasis is the most important feature of gastric cancer accounting for more than 90% of tumor-related mortality. As one of the main modulators of epithelial-mesenchymal transition (EMT), histone deacetylase inhibitors (HDACI) are considered rational candidates for cancer therapy. Valproic acid (VPA) is a HDACI with reported controversial effects on the EMT. The main aim of the current study was to evaluate the effects of VPA treatment on cell survival and EMT-related features of humangastric cancer cells (AGS). METHODS:Methyl-thiazoltetrazolium (MTT) assay was utilized to assess the effect of VPA on the proliferation rate of cells. Apoptotic cell death was detected with Annexin V/PI staining. Migratory ability of cells following VPA treatment was assessed using a Boyden chamber test. The expression of EMT markers in AGS cells was analyzed using quantitative real-time RT-PCR. RESULTS: Treatment with VPA significantly inhibited AGS cell proliferation compared with control. An increased rate of early and late apoptotic cells was observed following VPA exposure. It was demonstrated that VPA significantly diminished the cell migratory ability in AGS gastric cancer cells. Furthermore, treatment with VPA significantly decreased the expression of E-cadherin but increased the Vimentin expression. CONCLUSIONS: Our results showed that VPA induces apoptosis and inhibits the cell proliferation and the migratory ability of AGS gastric cancer cells and may prove useful in the development of therapeutic agents for humangastric cancer. However, these preliminary findings call for further investigations to clarify the precise molecular mechanisms by which VPA modulates the EMT process in a cell type-specific manner.
Authors: Alexandria M Haslehurst; Madhuri Koti; Moyez Dharsee; Paulo Nuin; Ken Evans; Joseph Geraci; Timothy Childs; Jian Chen; Jieran Li; Johanne Weberpals; Scott Davey; Jeremy Squire; Paul C Park; Harriet Feilotter Journal: BMC Cancer Date: 2012-03-19 Impact factor: 4.430