Stigmasterol inhibits cancer stem cell activity in endometrial cancer by repressing IGF1R/mTOR/AKT pathway

Endometrial cancer (EC) is a commonly diagnosed gynecological malignancy among women worldwide. Stigmasterol is a potential natural phytosterol present in vegetable oils and seeds with anti-cancer activity. We investigate the effects of stigmasterol on the malignant properties of EC cells and the in...

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Main Authors: Wen-Ling Wang, Shih-Ming Chen, Yueh-Chun Lee, Wen-Wei Chang
Format: Article
Language:English
Published: Elsevier 2022-12-01
Series:Journal of Functional Foods
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S175646462200408X
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author Wen-Ling Wang
Shih-Ming Chen
Yueh-Chun Lee
Wen-Wei Chang
author_facet Wen-Ling Wang
Shih-Ming Chen
Yueh-Chun Lee
Wen-Wei Chang
author_sort Wen-Ling Wang
collection DOAJ
description Endometrial cancer (EC) is a commonly diagnosed gynecological malignancy among women worldwide. Stigmasterol is a potential natural phytosterol present in vegetable oils and seeds with anti-cancer activity. We investigate the effects of stigmasterol on the malignant properties of EC cells and the involved molecular mechanisms. We found that stigmasterol inhibited the proliferation of EC cells according to MTT and colony formation assays. The anti-proliferative effect of stigmasterol was not suppressed by the inhibitors of apoptosis or reactive oxygen species, but was associated with G1 cell cycle arrest. In addition, stigmasterol reduced cell migration by inhibiting vimentin, SNAI1, SLUG, or ZEB1. Stigmasterol also suppressed tumorsphere formation and cancer stemness proteins including β-catenin, c-MYC, and OCT4, as well as the activation of IGF1R/AKT/mTOR pathway activation in EC cells. In conclusion, our study demonstrated that stigmasterol represses cell cycle progression, migration, and cancer stem cell activity in EC cells by inhibiting IGF1R/AKT/mTOR pathway.
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spelling doaj.art-8ebd015db0f54b09a086b82aabdcd9712022-12-22T02:57:28ZengElsevierJournal of Functional Foods1756-46462022-12-0199105338Stigmasterol inhibits cancer stem cell activity in endometrial cancer by repressing IGF1R/mTOR/AKT pathwayWen-Ling Wang0Shih-Ming Chen1Yueh-Chun Lee2Wen-Wei Chang3Department of Biomedical Sciences, Chung Shan Medical University, Taichung 402306, TaiwanBachelor Program in Health Care and Social Work for Indigenous Students, Providence University, Taichung 433719, TaiwanSchool of Medicine, Chung Shan Medical University, Taichung 402306, Taiwan; Radiation Oncology Department, Chung Shan Medical University Hospital, Taichung 402306, Taiwan; Corresponding authors at: School of Medicine, Chung Shan Medical University, Taichung 402306, Taiwan (Y.-C.L.); Department of Biomedical Sciences, Chung Shan Medical University, Taichung 402306, Taiwan (W.-W.C.).Department of Biomedical Sciences, Chung Shan Medical University, Taichung 402306, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402306, Taiwan; Corresponding authors at: School of Medicine, Chung Shan Medical University, Taichung 402306, Taiwan (Y.-C.L.); Department of Biomedical Sciences, Chung Shan Medical University, Taichung 402306, Taiwan (W.-W.C.).Endometrial cancer (EC) is a commonly diagnosed gynecological malignancy among women worldwide. Stigmasterol is a potential natural phytosterol present in vegetable oils and seeds with anti-cancer activity. We investigate the effects of stigmasterol on the malignant properties of EC cells and the involved molecular mechanisms. We found that stigmasterol inhibited the proliferation of EC cells according to MTT and colony formation assays. The anti-proliferative effect of stigmasterol was not suppressed by the inhibitors of apoptosis or reactive oxygen species, but was associated with G1 cell cycle arrest. In addition, stigmasterol reduced cell migration by inhibiting vimentin, SNAI1, SLUG, or ZEB1. Stigmasterol also suppressed tumorsphere formation and cancer stemness proteins including β-catenin, c-MYC, and OCT4, as well as the activation of IGF1R/AKT/mTOR pathway activation in EC cells. In conclusion, our study demonstrated that stigmasterol represses cell cycle progression, migration, and cancer stem cell activity in EC cells by inhibiting IGF1R/AKT/mTOR pathway.http://www.sciencedirect.com/science/article/pii/S175646462200408XStigmasterolPhytosterolEndometrial cancerIGF1RAKTmTOR
spellingShingle Wen-Ling Wang
Shih-Ming Chen
Yueh-Chun Lee
Wen-Wei Chang
Stigmasterol inhibits cancer stem cell activity in endometrial cancer by repressing IGF1R/mTOR/AKT pathway
Journal of Functional Foods
Stigmasterol
Phytosterol
Endometrial cancer
IGF1R
AKT
mTOR
title Stigmasterol inhibits cancer stem cell activity in endometrial cancer by repressing IGF1R/mTOR/AKT pathway
title_full Stigmasterol inhibits cancer stem cell activity in endometrial cancer by repressing IGF1R/mTOR/AKT pathway
title_fullStr Stigmasterol inhibits cancer stem cell activity in endometrial cancer by repressing IGF1R/mTOR/AKT pathway
title_full_unstemmed Stigmasterol inhibits cancer stem cell activity in endometrial cancer by repressing IGF1R/mTOR/AKT pathway
title_short Stigmasterol inhibits cancer stem cell activity in endometrial cancer by repressing IGF1R/mTOR/AKT pathway
title_sort stigmasterol inhibits cancer stem cell activity in endometrial cancer by repressing igf1r mtor akt pathway
topic Stigmasterol
Phytosterol
Endometrial cancer
IGF1R
AKT
mTOR
url http://www.sciencedirect.com/science/article/pii/S175646462200408X
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AT yuehchunlee stigmasterolinhibitscancerstemcellactivityinendometrialcancerbyrepressingigf1rmtoraktpathway
AT wenweichang stigmasterolinhibitscancerstemcellactivityinendometrialcancerbyrepressingigf1rmtoraktpathway