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Updated: Jan 25, 2026
Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples
Published on: October 2, 2020
Transcriptome-based identification of lovastatin as a breast cancer stem cell-targeting drug
Luz X Vásquez-Bochm1, Mireya Velázquez-Paniagua2, Sandra S Castro-Vázquez3
1Department of Pharmacology, School of Medicine, National Autonomous University of Mexico (Universidad Nacional Autónoma de México; UNAM), Mexico City, Mexico; Graduate Program in Chemical Sciences, UNAM, Mexico City, Mexico.
Background:
Breast cancer is a neoplastic disease with high morbidity and mortality in women worldwide. Breast cancer stem cells (CSCs) have a significant function in tumor growth, recurrence, and therapeutic resistance. Thus, CSCs have been pointed as targets of new therapies for breast cancer. Herein, we aimed to repurpose certain drugs as breast CSC-targeting agents.
Methods:
We compared a consensus breast CSC signature with the transcriptomic changes that were induced by over 1300 bioactive compounds using Connectivity Map. The effects of the selected drugs on SOX2 promoter transactivation, SOX2 expression, viability, clonogenicity, and ALDH activity in breast cancer cells were analyzed by luciferase assay, western blot, MTT assay, mammosphere formation assay, and ALDEFLUOR® test, respectively. Gene Set Enrichment Analysis (GSEA) was performed using the gene expression data from mammary tumors of mice that were treated with lovastatin.
Results:
Five drugs (fasudil, pivmecillinam, ursolic acid, 16,16-dimethylprostaglandin E2, and lovastatin) induced signatures that correlated negatively with the query CSC signature. In vitro, lovastatin inhibited SOX2 promoter transactivation, and reduced the efficiency of mammosphere formation and the percentage of ALDH+ cells. Mevalonate mitigated the effects of lovastatin, suggesting that the targeting of CSCs by lovastatin was mediated by the inhibition of its reported target, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR). By GSEA, lovastatin downregulated genes that are involved in stemness and invasiveness in mammary tumors, corroborating our in vitro findings.
Conclusion:
Lovastatin is a breast CSC-targeting drug. The inhibition of HMGCR might develop new adjuvant therapeutic strategies for breast tumors.
Insights
Lovastatin effectively targets breast cancer stem cells (CSCs) by inhibiting HMGCR. This repurposed drug shows potential for new adjuvant therapies against breast tumors, addressing recurrence and resistance.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Breast cancer remains a leading cause of mortality in women globally.
- Breast cancer stem cells (CSCs) drive tumor growth, recurrence, and treatment resistance.
- Targeting CSCs is a promising strategy for novel breast cancer therapies.
Purpose of the Study:
- To identify and repurpose existing drugs as novel agents targeting breast cancer stem cells.
- To evaluate the efficacy of identified drugs against CSC properties in vitro and in vivo.
Main Methods:
- Comparative transcriptomic analysis using Connectivity Map to screen over 1300 compounds against a CSC signature.
- In vitro assays including luciferase assay, western blot, MTT assay, mammosphere formation assay, and ALDEFLUOR® test to assess drug effects.
- Gene Set Enrichment Analysis (GSEA) on mouse mammary tumor data to evaluate lovastatin's in vivo impact.
Main Results:
- Five drugs, including lovastatin, exhibited signatures negatively correlated with the CSC signature.
- Lovastatin inhibited CSC markers (SOX2, ALDH activity) and mammosphere formation in vitro.
- Lovastatin's effects were mediated by HMGCR inhibition, and GSEA confirmed downregulation of stemness and invasiveness genes in vivo.
Conclusions:
- Lovastatin demonstrates significant potential as a breast cancer stem cell-targeting agent.
- Inhibition of HMGCR by lovastatin offers a potential pathway for developing new adjuvant therapeutic strategies for breast cancer.
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