N6-(2-hydroxyethyl)-Adenosine Induces Apoptosis via ER Stress and Autophagy of Gastric Carcinoma Cells In Vitro and In Vivo

Gastric cancer is the most common malignant tumor of the digestive tract and is great challenge in clinical treatment. N6-(2-Hydroxyethyl)-adenosine (HEA), widely present in various fungi, is a natural adenosine derivative with many biological and pharmacological activities. Here, we assessed the an...

Full description

Bibliographic Details
Main Authors: Hongqing Xie, Xiaotong Li, Weiwei Yang, Liping Yu, Xiasen Jiang, Yajie Chen, Zhangfei Shen, Conghui Li, Meier Gu, Liangen Shi
Format: Article
Language:English
Published: MDPI AG 2020-08-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/21/16/5815
_version_ 1797558378263740416
author Hongqing Xie
Xiaotong Li
Weiwei Yang
Liping Yu
Xiasen Jiang
Yajie Chen
Zhangfei Shen
Conghui Li
Meier Gu
Liangen Shi
author_facet Hongqing Xie
Xiaotong Li
Weiwei Yang
Liping Yu
Xiasen Jiang
Yajie Chen
Zhangfei Shen
Conghui Li
Meier Gu
Liangen Shi
author_sort Hongqing Xie
collection DOAJ
description Gastric cancer is the most common malignant tumor of the digestive tract and is great challenge in clinical treatment. N6-(2-Hydroxyethyl)-adenosine (HEA), widely present in various fungi, is a natural adenosine derivative with many biological and pharmacological activities. Here, we assessed the antineoplastic effect of HEA on gastric carcinoma. HEA exerted cytotoxic effects against gastric carcinoma cells (SGC-7901 and AGS) in a dose and time-dependent manner. Additionally, we found that HEA induced reactive oxygen species production and mitochondrial membrane potential depolarization. Moreover, it could trigger caspase-dependent apoptosis, promoting intracellular Ca<sup>2+</sup>-related endoplasmic reticulum (ER) stress and autophagy. On the other hand, HEA could significantly inhibit the growth of transplanted tumors in nude mice and induce apoptosis of tumor tissues cells in vivo. In conclusion, HEA induced apoptosis of gastric carcinoma cells in vitro and in vivo, demonstrating that HEA is a potential chemotherapeutic agent for gastric carcinoma.
first_indexed 2024-03-10T17:30:39Z
format Article
id doaj.art-6651cc834d9748e2a81766c2ec31efb0
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-03-10T17:30:39Z
publishDate 2020-08-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
spelling doaj.art-6651cc834d9748e2a81766c2ec31efb02023-11-20T10:02:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-012116581510.3390/ijms21165815N6-(2-hydroxyethyl)-Adenosine Induces Apoptosis via ER Stress and Autophagy of Gastric Carcinoma Cells In Vitro and In VivoHongqing Xie0Xiaotong Li1Weiwei Yang2Liping Yu3Xiasen Jiang4Yajie Chen5Zhangfei Shen6Conghui Li7Meier Gu8Liangen Shi9College of Animal Sciences, Zhejiang University, Hangzhou 310058, ChinaCollege of Animal Sciences, Zhejiang University, Hangzhou 310058, ChinaLaboratory Animal Center, Hangzhou Normal University, Hangzhou 311121, ChinaLaboratory Animal Center, Hangzhou Normal University, Hangzhou 311121, ChinaCollege of Animal Sciences, Zhejiang University, Hangzhou 310058, ChinaCollege of Animal Sciences, Zhejiang University, Hangzhou 310058, ChinaCollege of Animal Sciences, Zhejiang University, Hangzhou 310058, ChinaCollege of Animal Sciences, Zhejiang University, Hangzhou 310058, ChinaLaboratory Animal Center, Hangzhou Normal University, Hangzhou 311121, ChinaCollege of Animal Sciences, Zhejiang University, Hangzhou 310058, ChinaGastric cancer is the most common malignant tumor of the digestive tract and is great challenge in clinical treatment. N6-(2-Hydroxyethyl)-adenosine (HEA), widely present in various fungi, is a natural adenosine derivative with many biological and pharmacological activities. Here, we assessed the antineoplastic effect of HEA on gastric carcinoma. HEA exerted cytotoxic effects against gastric carcinoma cells (SGC-7901 and AGS) in a dose and time-dependent manner. Additionally, we found that HEA induced reactive oxygen species production and mitochondrial membrane potential depolarization. Moreover, it could trigger caspase-dependent apoptosis, promoting intracellular Ca<sup>2+</sup>-related endoplasmic reticulum (ER) stress and autophagy. On the other hand, HEA could significantly inhibit the growth of transplanted tumors in nude mice and induce apoptosis of tumor tissues cells in vivo. In conclusion, HEA induced apoptosis of gastric carcinoma cells in vitro and in vivo, demonstrating that HEA is a potential chemotherapeutic agent for gastric carcinoma.https://www.mdpi.com/1422-0067/21/16/5815N6-(2-Hydroxyethyl)-adenosineapoptosisendoplasmic reticulum stressgastric carcinomaautophagy
spellingShingle Hongqing Xie
Xiaotong Li
Weiwei Yang
Liping Yu
Xiasen Jiang
Yajie Chen
Zhangfei Shen
Conghui Li
Meier Gu
Liangen Shi
N6-(2-hydroxyethyl)-Adenosine Induces Apoptosis via ER Stress and Autophagy of Gastric Carcinoma Cells In Vitro and In Vivo
International Journal of Molecular Sciences
N6-(2-Hydroxyethyl)-adenosine
apoptosis
endoplasmic reticulum stress
gastric carcinoma
autophagy
title N6-(2-hydroxyethyl)-Adenosine Induces Apoptosis via ER Stress and Autophagy of Gastric Carcinoma Cells In Vitro and In Vivo
title_full N6-(2-hydroxyethyl)-Adenosine Induces Apoptosis via ER Stress and Autophagy of Gastric Carcinoma Cells In Vitro and In Vivo
title_fullStr N6-(2-hydroxyethyl)-Adenosine Induces Apoptosis via ER Stress and Autophagy of Gastric Carcinoma Cells In Vitro and In Vivo
title_full_unstemmed N6-(2-hydroxyethyl)-Adenosine Induces Apoptosis via ER Stress and Autophagy of Gastric Carcinoma Cells In Vitro and In Vivo
title_short N6-(2-hydroxyethyl)-Adenosine Induces Apoptosis via ER Stress and Autophagy of Gastric Carcinoma Cells In Vitro and In Vivo
title_sort n6 2 hydroxyethyl adenosine induces apoptosis via er stress and autophagy of gastric carcinoma cells in vitro and in vivo
topic N6-(2-Hydroxyethyl)-adenosine
apoptosis
endoplasmic reticulum stress
gastric carcinoma
autophagy
url https://www.mdpi.com/1422-0067/21/16/5815
work_keys_str_mv AT hongqingxie n62hydroxyethyladenosineinducesapoptosisviaerstressandautophagyofgastriccarcinomacellsinvitroandinvivo
AT xiaotongli n62hydroxyethyladenosineinducesapoptosisviaerstressandautophagyofgastriccarcinomacellsinvitroandinvivo
AT weiweiyang n62hydroxyethyladenosineinducesapoptosisviaerstressandautophagyofgastriccarcinomacellsinvitroandinvivo
AT lipingyu n62hydroxyethyladenosineinducesapoptosisviaerstressandautophagyofgastriccarcinomacellsinvitroandinvivo
AT xiasenjiang n62hydroxyethyladenosineinducesapoptosisviaerstressandautophagyofgastriccarcinomacellsinvitroandinvivo
AT yajiechen n62hydroxyethyladenosineinducesapoptosisviaerstressandautophagyofgastriccarcinomacellsinvitroandinvivo
AT zhangfeishen n62hydroxyethyladenosineinducesapoptosisviaerstressandautophagyofgastriccarcinomacellsinvitroandinvivo
AT conghuili n62hydroxyethyladenosineinducesapoptosisviaerstressandautophagyofgastriccarcinomacellsinvitroandinvivo
AT meiergu n62hydroxyethyladenosineinducesapoptosisviaerstressandautophagyofgastriccarcinomacellsinvitroandinvivo
AT liangenshi n62hydroxyethyladenosineinducesapoptosisviaerstressandautophagyofgastriccarcinomacellsinvitroandinvivo