Isorhamnetin Induces Apoptosis and Suppresses Metastasis of Human Endometrial Carcinoma Ishikawa Cells via Endoplasmic Reticulum Stress Promotion and Matrix Metalloproteinase-2/9 Inhibition In Vitro and In Vivo

Endometrial cancer (EC) is a very common female cancer which has attracted more and more attention. According to the individual patient’s condition, the current treatment of EC patients is mainly based on surgery, which is supplemented by chemotherapy, radiotherapy, and endocrine intervention. Howev...

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Main Authors: Lei Ye, Run-Hui Ma, Xiu-Xiu Zhang, Kiran Thakur, Jian-Guo Zhang, Mohammad Rizwan Khan, Rosa Busquets, Zhao-Jun Wei
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:Foods
Subjects:
Online Access:https://www.mdpi.com/2304-8158/11/21/3415
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author Lei Ye
Run-Hui Ma
Xiu-Xiu Zhang
Kiran Thakur
Jian-Guo Zhang
Mohammad Rizwan Khan
Rosa Busquets
Zhao-Jun Wei
author_facet Lei Ye
Run-Hui Ma
Xiu-Xiu Zhang
Kiran Thakur
Jian-Guo Zhang
Mohammad Rizwan Khan
Rosa Busquets
Zhao-Jun Wei
author_sort Lei Ye
collection DOAJ
description Endometrial cancer (EC) is a very common female cancer which has attracted more and more attention. According to the individual patient’s condition, the current treatment of EC patients is mainly based on surgery, which is supplemented by chemotherapy, radiotherapy, and endocrine intervention. However, these existing treatment strategies also have some inevitable limitations. Therefore, it is particularly important to find an active ingredient with low toxicity and a high safety profile against EC. Isorhamnetin is a flavonoid known to be present in a variety of plants, such as sea buckthorn, dry willow, and wolfberry. In recent years, the anti-tumor effects of isorhamnetin have been reported. In our study, isorhamnetin was shown to induce apoptosis in Ishikawa cells by inducing the endogenous mitochondrial apoptotic pathway and exogenous death receptor pathway, promoting the endoplasmic reticulum stress-related pathway, and activating the corresponding markers of UPR response. In addition, isorhamnetin affected the expression of MMP2 and MMP9-related proteins in vitro and in vivo and eventually repressed metastasis. Therefore, isorhamnetin can be used as a promising medicinal material for the treatment of EC.
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spelling doaj.art-d4d0c9ec0193432eb2c77aabce2969392023-11-24T04:40:26ZengMDPI AGFoods2304-81582022-10-011121341510.3390/foods11213415Isorhamnetin Induces Apoptosis and Suppresses Metastasis of Human Endometrial Carcinoma Ishikawa Cells via Endoplasmic Reticulum Stress Promotion and Matrix Metalloproteinase-2/9 Inhibition In Vitro and In VivoLei Ye0Run-Hui Ma1Xiu-Xiu Zhang2Kiran Thakur3Jian-Guo Zhang4Mohammad Rizwan Khan5Rosa Busquets6Zhao-Jun Wei7School of Food Science and Biological Engineering, Hefei University of Technology, Hefei 230009, ChinaSchool of Food Science and Biological Engineering, Hefei University of Technology, Hefei 230009, ChinaSchool of Food Science and Biological Engineering, Hefei University of Technology, Hefei 230009, ChinaSchool of Food Science and Biological Engineering, Hefei University of Technology, Hefei 230009, ChinaSchool of Food Science and Biological Engineering, Hefei University of Technology, Hefei 230009, ChinaDepartment of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi ArabiaSchool of Life Sciences, Pharmacy and Chemistry, Kingston University London, London KT1 2EE, UKSchool of Food Science and Biological Engineering, Hefei University of Technology, Hefei 230009, ChinaEndometrial cancer (EC) is a very common female cancer which has attracted more and more attention. According to the individual patient’s condition, the current treatment of EC patients is mainly based on surgery, which is supplemented by chemotherapy, radiotherapy, and endocrine intervention. However, these existing treatment strategies also have some inevitable limitations. Therefore, it is particularly important to find an active ingredient with low toxicity and a high safety profile against EC. Isorhamnetin is a flavonoid known to be present in a variety of plants, such as sea buckthorn, dry willow, and wolfberry. In recent years, the anti-tumor effects of isorhamnetin have been reported. In our study, isorhamnetin was shown to induce apoptosis in Ishikawa cells by inducing the endogenous mitochondrial apoptotic pathway and exogenous death receptor pathway, promoting the endoplasmic reticulum stress-related pathway, and activating the corresponding markers of UPR response. In addition, isorhamnetin affected the expression of MMP2 and MMP9-related proteins in vitro and in vivo and eventually repressed metastasis. Therefore, isorhamnetin can be used as a promising medicinal material for the treatment of EC.https://www.mdpi.com/2304-8158/11/21/3415endometrial cancerIshikawaisorhamnetinUPR responsemitochondria
spellingShingle Lei Ye
Run-Hui Ma
Xiu-Xiu Zhang
Kiran Thakur
Jian-Guo Zhang
Mohammad Rizwan Khan
Rosa Busquets
Zhao-Jun Wei
Isorhamnetin Induces Apoptosis and Suppresses Metastasis of Human Endometrial Carcinoma Ishikawa Cells via Endoplasmic Reticulum Stress Promotion and Matrix Metalloproteinase-2/9 Inhibition In Vitro and In Vivo
Foods
endometrial cancer
Ishikawa
isorhamnetin
UPR response
mitochondria
title Isorhamnetin Induces Apoptosis and Suppresses Metastasis of Human Endometrial Carcinoma Ishikawa Cells via Endoplasmic Reticulum Stress Promotion and Matrix Metalloproteinase-2/9 Inhibition In Vitro and In Vivo
title_full Isorhamnetin Induces Apoptosis and Suppresses Metastasis of Human Endometrial Carcinoma Ishikawa Cells via Endoplasmic Reticulum Stress Promotion and Matrix Metalloproteinase-2/9 Inhibition In Vitro and In Vivo
title_fullStr Isorhamnetin Induces Apoptosis and Suppresses Metastasis of Human Endometrial Carcinoma Ishikawa Cells via Endoplasmic Reticulum Stress Promotion and Matrix Metalloproteinase-2/9 Inhibition In Vitro and In Vivo
title_full_unstemmed Isorhamnetin Induces Apoptosis and Suppresses Metastasis of Human Endometrial Carcinoma Ishikawa Cells via Endoplasmic Reticulum Stress Promotion and Matrix Metalloproteinase-2/9 Inhibition In Vitro and In Vivo
title_short Isorhamnetin Induces Apoptosis and Suppresses Metastasis of Human Endometrial Carcinoma Ishikawa Cells via Endoplasmic Reticulum Stress Promotion and Matrix Metalloproteinase-2/9 Inhibition In Vitro and In Vivo
title_sort isorhamnetin induces apoptosis and suppresses metastasis of human endometrial carcinoma ishikawa cells via endoplasmic reticulum stress promotion and matrix metalloproteinase 2 9 inhibition in vitro and in vivo
topic endometrial cancer
Ishikawa
isorhamnetin
UPR response
mitochondria
url https://www.mdpi.com/2304-8158/11/21/3415
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