Ursolic Acid Decreases the Proliferation of MCF-7 Cell-Derived Breast Cancer Stem-Like Cells by Modulating the ERK and PI3K/AKT Signaling Pathways

Cancer stem cells are strong drivers of metastasis and cancer relapse, which makes them important therapeutic targets. Ursolic acid (UA), a pentacyclic triterpenoid, has anticancer effects in various types of cancer; however, little is known about its effect on the growth of MCF-7 cell-derived breas...

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Published inPreventive nutrition and food science Vol. 26; no. 4; pp. 434 - 444
Main Author Kim, Gi Dae
Format Journal Article
LanguageEnglish
Published Korea (South) 한국식품영양과학회 31.12.2021
The Korean Society of Food Science and Nutrition
Subjects
Original
식품과학
MCF-7 cell-derived breast cancer stem-like cells
ERK
PI3K/AKT
ursolic acid
Online AccessGet full text
ISSN2287-1098
2287-8602
DOI10.3746/pnf.2021.26.4.434

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Abstract Cancer stem cells are strong drivers of metastasis and cancer relapse, which makes them important therapeutic targets. Ursolic acid (UA), a pentacyclic triterpenoid, has anticancer effects in various types of cancer; however, little is known about its effect on the growth of MCF-7 cell-derived breast cancer stem (BCS)-like cells in estrogen receptor positive breast cancer. In this study, the anticancer activity of UA in MCF-7 cell-derived BCS-like cells and its mechanism of action were evaluated. Furthermore, its inhibitory effects on the proliferation of MCF-7 cell-derived BCS-like cells were compared with that on MCF-7 cells. In MCF-7 cells, UA increased p53 and p21 expression but decreased cyclin D, cyclin E, CDK4, and CDK2 expression to induce cell cycle arrest in the G0/G1 phase. Moreover, UA significantly suppressed migration, invasion, and colony formation in MCF-7 cells, and suppressed mammosphere formation in a concentration- dependent manner. In MCF-7 cell-derived BCS-like cells, UA significantly decreased migration, suppressed p-PI3K, p-AKT, and p-ERK expression, and enhanced p-FoxO1/FoxO3a expression. Accordingly, in MCF-7 cell-derived BCS-like cells, UA suppressed proliferation in part by downregulating ERK and PI3K/AKT signaling pathways. These findings provide the first evidence for the selective effects of UA in BCSs.
AbstractList Cancer stem cells are strong drivers of metastasis and cancer relapse, which makes them important therapeutic targets. Ursolic acid (UA), a pentacyclic triterpenoid, has anticancer effects in various types of cancer; however, little is known about its effect on the growth of MCF-7 cell-derived breast cancer stem (BCS)-like cells in estrogen receptor positive breast cancer. In this study, the anticancer activity of UA in MCF-7 cell-derived BCS-like cells and its mechanism of action were evaluated. Furthermore, its inhibitory effects on the proliferation of MCF-7 cell-derived BCS-like cells were compared with that on MCF-7 cells. In MCF-7 cells, UA increased p53 and p21 expression but decreased cyclin D, cyclin E, CDK4, and CDK2 expression to induce cell cycle arrest in the G0/G1 phase. Moreover, UA significantly suppressed migration, invasion, and colony formation in MCF-7 cells, and suppressed mammosphere formation in a concentration- dependent manner. In MCF-7 cell-derived BCS-like cells, UA significantly decreased migration, suppressed p-PI3K, p-AKT, and p-ERK expression, and enhanced p-FoxO1/FoxO3a expression. Accordingly, in MCF-7 cell-derived BCS-like cells, UA suppressed proliferation in part by downregulating ERK and PI3K/AKT signaling pathways. These findings provide the first evidence for the selective effects of UA in BCSs.Cancer stem cells are strong drivers of metastasis and cancer relapse, which makes them important therapeutic targets. Ursolic acid (UA), a pentacyclic triterpenoid, has anticancer effects in various types of cancer; however, little is known about its effect on the growth of MCF-7 cell-derived breast cancer stem (BCS)-like cells in estrogen receptor positive breast cancer. In this study, the anticancer activity of UA in MCF-7 cell-derived BCS-like cells and its mechanism of action were evaluated. Furthermore, its inhibitory effects on the proliferation of MCF-7 cell-derived BCS-like cells were compared with that on MCF-7 cells. In MCF-7 cells, UA increased p53 and p21 expression but decreased cyclin D, cyclin E, CDK4, and CDK2 expression to induce cell cycle arrest in the G0/G1 phase. Moreover, UA significantly suppressed migration, invasion, and colony formation in MCF-7 cells, and suppressed mammosphere formation in a concentration- dependent manner. In MCF-7 cell-derived BCS-like cells, UA significantly decreased migration, suppressed p-PI3K, p-AKT, and p-ERK expression, and enhanced p-FoxO1/FoxO3a expression. Accordingly, in MCF-7 cell-derived BCS-like cells, UA suppressed proliferation in part by downregulating ERK and PI3K/AKT signaling pathways. These findings provide the first evidence for the selective effects of UA in BCSs.
Cancer stem cells are strong drivers of metastasis and cancer relapse, which makes them important therapeutic targets. Ursolic acid (UA), a pentacyclic triterpenoid, has anticancer effects in various types of cancer; however, little is known about its effect on the growth of MCF-7 cell-derived breast cancer stem (BCS)-like cells in estrogen receptor positive breast cancer. In this study, the anticancer activity of UA in MCF-7 cell-derived BCS-like cells and its mechanism of action were evaluated. Furthermore, its inhibitory effects on the proliferation of MCF-7 cell-derived BCS-like cells were compared with that on MCF-7 cells. In MCF-7 cells, UA increased p53 and p21 expression but decreased cyclin D, cyclin E, CDK4, and CDK2 expression to induce cell cycle arrest in the G0/G1 phase. Moreover, UA significantly suppressed migration, invasion, and colony formation in MCF-7 cells, and suppressed mammosphere formation in a concentration- dependent manner. In MCF-7 cell-derived BCS-like cells, UA significantly decreased migration, suppressed p-PI3K, p-AKT, and p-ERK expression, and enhanced p-FoxO1/FoxO3a expression. Accordingly, in MCF-7 cell-derived BCS-like cells, UA suppressed proliferation in part by downregulating ERK and PI3K/AKT signaling pathways. These findings provide the first evidence for the selective effects of UA in BCSs.
Cancer stem cells are strong drivers of metastasis and cancer relapse, which makes them important therapeutic targets. Ursolic acid (UA), a pentacyclic triterpenoid, has anticancer effects in various types of cancer; however, little is known about its effect on the growth of MCF-7 cell-derived breast cancer stem (BCS)-like cells in estrogen receptor positive breast cancer. In this study, the anticancer activity of UA in MCF-7 cell-derived BCS-like cells and its mechanism of action were evaluated. Furthermore, its inhibitory effects on the proliferation of MCF-7 cell-derived BCS-like cells were compared with that on MCF-7 cells. In MCF-7 cells, UA increased p53 and p21 expression but decreased cyclin D, cyclin E, CDK4, and CDK2 expression to induce cell cycle arrest in the G0/G1 phase. Moreover, UA significantly suppressed migration, invasion, and colony formation in MCF-7 cells, and suppressed mammosphere formation in a concentration-dependent manner. In MCF-7 cell-derived BCS-like cells, UA significantly decreased migration, suppressed p-PI3K, p-AKT, and p-ERK expression, and enhanced p-FoxO1/FoxO3a expression. Accordingly, in MCF-7 cell-derived BCS-like cells, UA suppressed proliferation in part by downregulating ERK and PI3K/AKT signaling pathways. These findings provide the first evidence for the selective effects of UA in BCSs. KCI Citation Count: 1
Author Gi Dae Kim
AuthorAffiliation Department of Food and Nutrition, Kyungnam University, Gyeongnam 51767, Korea
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Keywords MCF-7 cell-derived breast cancer stem-like cells
ERK
PI3K/AKT
ursolic acid
Language English
License Copyright © 2021 by The Korean Society of Food Science and Nutrition.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Snippet Cancer stem cells are strong drivers of metastasis and cancer relapse, which makes them important therapeutic targets. Ursolic acid (UA), a pentacyclic...
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Title Ursolic Acid Decreases the Proliferation of MCF-7 Cell-Derived Breast Cancer Stem-Like Cells by Modulating the ERK and PI3K/AKT Signaling Pathways
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