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Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples
Published on: October 2, 2020
Ginsenoside Rg3 decreases breast cancer stem-like phenotypes through impairing MYC mRNA stability
Jin-Yue Ning1, Zi-Han Zhang2, Jia Zhang3
1Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian Medical University Dalian 116011, Liaoning, China.
Abstract:
Breast cancer stem cells (BCSCs) are responsible for breast cancer metastasis, recurrence and treatment resistance, all of which make BCSCs potential drivers of breast cancer aggression. Ginsenoside Rg3, a traditional Chinese herbal medicine, was reported to have multiple antitumor functions. Here, we revealed a novel effect of Rg3 on BCSCs. Rg3 inhibits breast cancer cell viability in a dose- and time-dependent manner. Importantly, Rg3 suppressed mammosphere formation, reduced the expression of stemness-related transcription factors, including c-Myc, Oct4, Sox2 and Lin28, and diminished ALDH(+) populations. Moreover, tumor-bearing mice treated with Rg3 exhibited robust delay of tumor growth and a decrease in tumor-initiating frequency. In addition, we found that Rg3 suppressed breast cancer stem-like properties mainly through inhibiting MYC expression. Mechanistically, Rg3 accelerated the degradation of MYC mRNA by enhancing the expression of the let-7 family, which was demonstrated to bind to the MYC 3' untranslated region (UTR). In conclusion, our findings reveal the remarkable suppressive effect of Rg3 on BCSCs, suggesting that Rg3 is a promising therapeutic treatment for breast cancer.
Insights
Ginsenoside Rg3 effectively inhibits breast cancer stem cells (BCSCs), reducing tumor growth and metastasis. This natural compound targets key stemness factors, offering a promising new avenue for breast cancer treatment.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Breast cancer stem cells (BCSCs) drive tumor metastasis, recurrence, and treatment resistance.
- Ginsenoside Rg3 is a compound from traditional Chinese medicine with known antitumor properties.
Purpose of the Study:
- To investigate the novel effects of Ginsenoside Rg3 on breast cancer stem cells.
- To elucidate the mechanisms by which Rg3 impacts BCSCs and breast cancer progression.
Main Methods:
- Assessing Rg3's effect on breast cancer cell viability, mammosphere formation, and stemness marker expression (c-Myc, Oct4, Sox2, Lin28, ALDH+).
- Evaluating Rg3's impact on tumor growth and tumor-initiating frequency in vivo.
- Investigating the molecular mechanism involving MYC mRNA degradation and let-7 family expression.
Main Results:
- Rg3 inhibited breast cancer cell viability, mammosphere formation, and reduced stemness markers.
- Rg3 treatment delayed tumor growth and decreased tumor-initiating frequency in mice.
- Rg3 suppressed BCSCs by inhibiting MYC expression via enhanced let-7 family-mediated mRNA degradation.
Conclusions:
- Ginsenoside Rg3 demonstrates a significant suppressive effect on breast cancer stem cells.
- Rg3's mechanism involves targeting MYC expression through the let-7 pathway.
- Ginsenoside Rg3 presents a promising therapeutic candidate for breast cancer treatment.
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