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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Format: | Article |
Language: | English |
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Elsevier
2022-12-01
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Series: | Journal of Functional Foods |
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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. |
first_indexed | 2024-04-13T06:48:31Z |
format | Article |
id | doaj.art-8ebd015db0f54b09a086b82aabdcd971 |
institution | Directory Open Access Journal |
issn | 1756-4646 |
language | English |
last_indexed | 2024-04-13T06:48:31Z |
publishDate | 2022-12-01 |
publisher | Elsevier |
record_format | Article |
series | Journal of Functional Foods |
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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