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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...

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Autores principales: Kyaw, Myat Tin Htwe, Yamaguchi, Yuya, Choijookhuu, Narantsog, Yano, Koichi, Takagi, Hideaki, Takahashi, Nobuyasu, Synn Oo, Phyu, Sato, Katsuaki, Hishikawa, Yoshitaka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY 2019
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.
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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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