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Inhibitory Effects of Ursolic Acid on the Stemness and Progression of Human Breast Cancer Cells by Modulating Argonaute-2.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2022 Dec 26; Vol. 24 (1). Date of Electronic Publication: 2022 Dec 26. - Publication Year :
- 2022
-
Abstract
- The stemness and metastasis of cancer cells are crucial features in determining cancer progression. Argonaute-2 (AGO2) overexpression was reported to be associated with microRNA (miRNA) biogenesis, supporting the self-renewal and differentiation characteristics of cancer stem cells (CSCs). Ursolic acid (UA), a triterpene compound, has multiple biological functions, including anticancer activity. In this study, we find that UA inhibits the proliferation of MDA-MB-231 and MCF-7 breast cancer cell lines using the CCK-8 assay. UA induced a significant decrease in the fraction of CSC in which it was examined by changes in the expression of stemness biomarkers, including the Nanog and Oct4 genes. UA altered invasion and migration capacities by significant decreases in the levels of epithelial-to-mesenchymal transition (EMT) proteins of slug and vimentin. Furthermore, the co-reduction in oncogenic miRNA levels ( miR - 9 and miR - 221 ) was a result of the down-modulation in AGO2 in breast cancer cells in vitro. Mechanically, UA increases PTEN expression to inactivate the FAK/PI3K/Akt/mTOR signaling pathway and the decreased level of c-Myc in quantitative RT-PCR and Western blot imaging analyses. Our current understanding of the anticancer potential of UA in interrupting between EMT programming and the state of CSC suggests that UA can contribute to improvements in the clinical practice of breast cancer.
- Subjects :
- Humans
Female
Phosphatidylinositol 3-Kinases metabolism
Cell Line, Tumor
Epithelial-Mesenchymal Transition genetics
Neoplastic Stem Cells metabolism
Cell Movement
Cell Proliferation
Gene Expression Regulation, Neoplastic
Ursolic Acid
Breast Neoplasms drug therapy
Breast Neoplasms genetics
Breast Neoplasms metabolism
MicroRNAs metabolism
Triterpenes pharmacology
Triterpenes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 24
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 36613808
- Full Text :
- https://doi.org/10.3390/ijms24010366