Hesperidin Reversed Long-Term <i>N</i>-methyl-<i>N</i>-nitro-<i>N</i>-Nitroguanidine Exposure Induced EMT and Cell Proliferation by Activating Autophagy in Gastric Tissues of Rats

Gastric cancer is a common malignant tumor worldwide. <i>N</i>-methyl-<i>N</i>-nitro-<i>N</i>-nitroguanidine (MNNG) is one of the most important inducing factors of gastric cancer. Autophagy can affect the occurrence and development of gastric cancer, but the mech...

Full description

Bibliographic Details
Main Authors: Zhaofeng Liang, Jiajia Song, Yumeng Xu, Xinyi Zhang, Yue Zhang, Hui Qian
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/14/24/5281
_version_ 1797455876830789632
author Zhaofeng Liang
Jiajia Song
Yumeng Xu
Xinyi Zhang
Yue Zhang
Hui Qian
author_facet Zhaofeng Liang
Jiajia Song
Yumeng Xu
Xinyi Zhang
Yue Zhang
Hui Qian
author_sort Zhaofeng Liang
collection DOAJ
description Gastric cancer is a common malignant tumor worldwide. <i>N</i>-methyl-<i>N</i>-nitro-<i>N</i>-nitroguanidine (MNNG) is one of the most important inducing factors of gastric cancer. Autophagy can affect the occurrence and development of gastric cancer, but the mechanism is not clear. Chemoprevention has been shown to be a rational and very promising approach to the prevention of gastric cancer. Hesperidin is a citrus flavone, an abundant polyphenol in citrus fruits and traditional Chinese medicine. It has an excellent phytochemistry that plays an intervention role in gastric cancer. However, it is unclear whether long-term exposure to MNNG will affect the occurrence of gastric cancer by regulating autophagy and whether hesperidin can play an intervention role in this process. In the present study, we demonstrated that long-term MNNG exposure inhibits autophagy in stomach tissues of rats, promotes the epithelial–mesenchymal transition (EMT) process and cell proliferation and suppresses the activity of the PI3K/AKT pathway. We further found that after rapamycin-activated autophagy, long-term MNNG exposure promoted cell proliferation and EMT were inhibited. In addition, hesperidin promotes autophagy and the activity of the PI3K/AKT pathway, as well as the suppression of proliferation and EMT in the stomach tissues of rats. Our findings indicate that hesperidin reverses MNNG-induced gastric cancer by activating autophagy and the PI3K/AKT pathway, which may provide a new basis for the early prevention and treatment of MNNG-induced gastric cancer.
first_indexed 2024-03-09T16:00:30Z
format Article
id doaj.art-96fd695d53de4dfa909731d8f1879634
institution Directory Open Access Journal
issn 2072-6643
language English
last_indexed 2024-03-09T16:00:30Z
publishDate 2022-12-01
publisher MDPI AG
record_format Article
series Nutrients
spelling doaj.art-96fd695d53de4dfa909731d8f18796342023-11-24T17:08:36ZengMDPI AGNutrients2072-66432022-12-011424528110.3390/nu14245281Hesperidin Reversed Long-Term <i>N</i>-methyl-<i>N</i>-nitro-<i>N</i>-Nitroguanidine Exposure Induced EMT and Cell Proliferation by Activating Autophagy in Gastric Tissues of RatsZhaofeng Liang0Jiajia Song1Yumeng Xu2Xinyi Zhang3Yue Zhang4Hui Qian5Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Wujin Hospital Affiliated of Jiangsu University, Changzhou 213017, ChinaDepartment of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, ChinaDepartment of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, ChinaDepartment of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, ChinaDepartment of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, ChinaWujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Wujin Hospital Affiliated of Jiangsu University, Changzhou 213017, ChinaGastric cancer is a common malignant tumor worldwide. <i>N</i>-methyl-<i>N</i>-nitro-<i>N</i>-nitroguanidine (MNNG) is one of the most important inducing factors of gastric cancer. Autophagy can affect the occurrence and development of gastric cancer, but the mechanism is not clear. Chemoprevention has been shown to be a rational and very promising approach to the prevention of gastric cancer. Hesperidin is a citrus flavone, an abundant polyphenol in citrus fruits and traditional Chinese medicine. It has an excellent phytochemistry that plays an intervention role in gastric cancer. However, it is unclear whether long-term exposure to MNNG will affect the occurrence of gastric cancer by regulating autophagy and whether hesperidin can play an intervention role in this process. In the present study, we demonstrated that long-term MNNG exposure inhibits autophagy in stomach tissues of rats, promotes the epithelial–mesenchymal transition (EMT) process and cell proliferation and suppresses the activity of the PI3K/AKT pathway. We further found that after rapamycin-activated autophagy, long-term MNNG exposure promoted cell proliferation and EMT were inhibited. In addition, hesperidin promotes autophagy and the activity of the PI3K/AKT pathway, as well as the suppression of proliferation and EMT in the stomach tissues of rats. Our findings indicate that hesperidin reverses MNNG-induced gastric cancer by activating autophagy and the PI3K/AKT pathway, which may provide a new basis for the early prevention and treatment of MNNG-induced gastric cancer.https://www.mdpi.com/2072-6643/14/24/5281gastric cancerMNNGhesperidinautophagyPI3K/AKT
spellingShingle Zhaofeng Liang
Jiajia Song
Yumeng Xu
Xinyi Zhang
Yue Zhang
Hui Qian
Hesperidin Reversed Long-Term <i>N</i>-methyl-<i>N</i>-nitro-<i>N</i>-Nitroguanidine Exposure Induced EMT and Cell Proliferation by Activating Autophagy in Gastric Tissues of Rats
Nutrients
gastric cancer
MNNG
hesperidin
autophagy
PI3K/AKT
title Hesperidin Reversed Long-Term <i>N</i>-methyl-<i>N</i>-nitro-<i>N</i>-Nitroguanidine Exposure Induced EMT and Cell Proliferation by Activating Autophagy in Gastric Tissues of Rats
title_full Hesperidin Reversed Long-Term <i>N</i>-methyl-<i>N</i>-nitro-<i>N</i>-Nitroguanidine Exposure Induced EMT and Cell Proliferation by Activating Autophagy in Gastric Tissues of Rats
title_fullStr Hesperidin Reversed Long-Term <i>N</i>-methyl-<i>N</i>-nitro-<i>N</i>-Nitroguanidine Exposure Induced EMT and Cell Proliferation by Activating Autophagy in Gastric Tissues of Rats
title_full_unstemmed Hesperidin Reversed Long-Term <i>N</i>-methyl-<i>N</i>-nitro-<i>N</i>-Nitroguanidine Exposure Induced EMT and Cell Proliferation by Activating Autophagy in Gastric Tissues of Rats
title_short Hesperidin Reversed Long-Term <i>N</i>-methyl-<i>N</i>-nitro-<i>N</i>-Nitroguanidine Exposure Induced EMT and Cell Proliferation by Activating Autophagy in Gastric Tissues of Rats
title_sort hesperidin reversed long term i n i methyl i n i nitro i n i nitroguanidine exposure induced emt and cell proliferation by activating autophagy in gastric tissues of rats
topic gastric cancer
MNNG
hesperidin
autophagy
PI3K/AKT
url https://www.mdpi.com/2072-6643/14/24/5281
work_keys_str_mv AT zhaofengliang hesperidinreversedlongterminimethylininitroininitroguanidineexposureinducedemtandcellproliferationbyactivatingautophagyingastrictissuesofrats
AT jiajiasong hesperidinreversedlongterminimethylininitroininitroguanidineexposureinducedemtandcellproliferationbyactivatingautophagyingastrictissuesofrats
AT yumengxu hesperidinreversedlongterminimethylininitroininitroguanidineexposureinducedemtandcellproliferationbyactivatingautophagyingastrictissuesofrats
AT xinyizhang hesperidinreversedlongterminimethylininitroininitroguanidineexposureinducedemtandcellproliferationbyactivatingautophagyingastrictissuesofrats
AT yuezhang hesperidinreversedlongterminimethylininitroininitroguanidineexposureinducedemtandcellproliferationbyactivatingautophagyingastrictissuesofrats
AT huiqian hesperidinreversedlongterminimethylininitroininitroguanidineexposureinducedemtandcellproliferationbyactivatingautophagyingastrictissuesofrats