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The HDAC Inhibitor, SAHA, Combined with Cisplatin Synergistically Induces Apoptosis in Alpha-fetoprotein-producing Hepatoid Adenocarcinoma Cells
Hepatoid adenocarcinoma (HAC) is a rare and aggressive gastrointestinal tract cancer that is characterized by hepatic differentiation and production of alpha-fetoprotein (AFP). Cisplatin is mainly used to treat HAC, but the efficacy is poor. Recently, the histone deacetylase inhibitor, suberoylanili...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434315/ https://www.ncbi.nlm.nih.gov/pubmed/30923410 http://dx.doi.org/10.1267/ahc.18044 |
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author | Kyaw, Myat Tin Htwe Yamaguchi, Yuya Choijookhuu, Narantsog Yano, Koichi Takagi, Hideaki Takahashi, Nobuyasu Synn Oo, Phyu Sato, Katsuaki Hishikawa, Yoshitaka |
author_facet | Kyaw, Myat Tin Htwe Yamaguchi, Yuya Choijookhuu, Narantsog Yano, Koichi Takagi, Hideaki Takahashi, Nobuyasu Synn Oo, Phyu Sato, Katsuaki Hishikawa, Yoshitaka |
author_sort | Kyaw, Myat Tin Htwe |
collection | PubMed |
description | Hepatoid adenocarcinoma (HAC) is a rare and aggressive gastrointestinal tract cancer that is characterized by hepatic differentiation and production of alpha-fetoprotein (AFP). Cisplatin is mainly used to treat HAC, but the efficacy is poor. Recently, the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), was approved as an anticancer agent. In this study, we investigated the anticancer effect of SAHA in combination with cisplatin in VAT-39 cells, a newly established HAC cell line. Cell viability and apoptosis were examined by MTT assay, flow cytometry and TUNEL assay. Expression of H3S10, cleaved caspase-3, Bax, and Bcl-2 were evaluated by immunohistochemistry and western blotting. AFP levels were examined in VAT-39 cells and culture medium. Combined treatment with cisplatin and SAHA efficiently inhibited cell proliferation and decreased cell viability. Apoptotic cells, but not necrotic cells, were significantly increased following the combined treatment, and an increase in the Bax/Bcl-2 ratio indicated that the combination of cisplatin and SAHA induced apoptosis through the mitochondrial pathway. VAT-39 cells treated with cisplatin and SAHA also partially lost their main characteristic of AFP production. We conclude that cisplatin and SAHA have a synergistic anticancer effect of inducing apoptosis, and that this combination treatment may be effective for HAC. |
format | Online Article Text |
id | pubmed-6434315 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY |
record_format | MEDLINE/PubMed |
spelling | pubmed-64343152019-03-28 The HDAC Inhibitor, SAHA, Combined with Cisplatin Synergistically Induces Apoptosis in Alpha-fetoprotein-producing Hepatoid Adenocarcinoma Cells Kyaw, Myat Tin Htwe Yamaguchi, Yuya Choijookhuu, Narantsog Yano, Koichi Takagi, Hideaki Takahashi, Nobuyasu Synn Oo, Phyu Sato, Katsuaki Hishikawa, Yoshitaka Acta Histochem Cytochem Regular Article Hepatoid adenocarcinoma (HAC) is a rare and aggressive gastrointestinal tract cancer that is characterized by hepatic differentiation and production of alpha-fetoprotein (AFP). Cisplatin is mainly used to treat HAC, but the efficacy is poor. Recently, the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), was approved as an anticancer agent. In this study, we investigated the anticancer effect of SAHA in combination with cisplatin in VAT-39 cells, a newly established HAC cell line. Cell viability and apoptosis were examined by MTT assay, flow cytometry and TUNEL assay. Expression of H3S10, cleaved caspase-3, Bax, and Bcl-2 were evaluated by immunohistochemistry and western blotting. AFP levels were examined in VAT-39 cells and culture medium. Combined treatment with cisplatin and SAHA efficiently inhibited cell proliferation and decreased cell viability. Apoptotic cells, but not necrotic cells, were significantly increased following the combined treatment, and an increase in the Bax/Bcl-2 ratio indicated that the combination of cisplatin and SAHA induced apoptosis through the mitochondrial pathway. VAT-39 cells treated with cisplatin and SAHA also partially lost their main characteristic of AFP production. We conclude that cisplatin and SAHA have a synergistic anticancer effect of inducing apoptosis, and that this combination treatment may be effective for HAC. JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY 2019-02-28 2019-02-23 /pmc/articles/PMC6434315/ /pubmed/30923410 http://dx.doi.org/10.1267/ahc.18044 Text en 2019 The Japan Society of Histochemistry and Cytochemistry This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Regular Article Kyaw, Myat Tin Htwe Yamaguchi, Yuya Choijookhuu, Narantsog Yano, Koichi Takagi, Hideaki Takahashi, Nobuyasu Synn Oo, Phyu Sato, Katsuaki Hishikawa, Yoshitaka The HDAC Inhibitor, SAHA, Combined with Cisplatin Synergistically Induces Apoptosis in Alpha-fetoprotein-producing Hepatoid Adenocarcinoma Cells |
title | The HDAC Inhibitor, SAHA, Combined with Cisplatin Synergistically Induces Apoptosis in Alpha-fetoprotein-producing Hepatoid Adenocarcinoma Cells |
title_full | The HDAC Inhibitor, SAHA, Combined with Cisplatin Synergistically Induces Apoptosis in Alpha-fetoprotein-producing Hepatoid Adenocarcinoma Cells |
title_fullStr | The HDAC Inhibitor, SAHA, Combined with Cisplatin Synergistically Induces Apoptosis in Alpha-fetoprotein-producing Hepatoid Adenocarcinoma Cells |
title_full_unstemmed | The HDAC Inhibitor, SAHA, Combined with Cisplatin Synergistically Induces Apoptosis in Alpha-fetoprotein-producing Hepatoid Adenocarcinoma Cells |
title_short | The HDAC Inhibitor, SAHA, Combined with Cisplatin Synergistically Induces Apoptosis in Alpha-fetoprotein-producing Hepatoid Adenocarcinoma Cells |
title_sort | hdac inhibitor, saha, combined with cisplatin synergistically induces apoptosis in alpha-fetoprotein-producing hepatoid adenocarcinoma cells |
topic | Regular Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434315/ https://www.ncbi.nlm.nih.gov/pubmed/30923410 http://dx.doi.org/10.1267/ahc.18044 |
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