ArticlePloS one2019
Metformin exhibited anticancer activity by lowering cellular cholesterol content in breast cancer cells.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 66 citations in OpenAlex.
- Antiproliferative Mechanisms of Metformin in Breast Cancer: A Systematic Review of the Literature.International journal of molecular sciences · 2024Pooled it
- Cholesterol homeostasis and cancer: a new perspective on the low-density lipoprotein receptor.Cellular oncology (Dordrecht, Netherlands) · 2022Pooled it
- Trial
- Cholesterol-Lowering Treatment Blocks Epithelial-Mesenchymal Transition (EMT) Associated Invasiveness and Drug Resistance in Breast and Colorectal Adenocarcinoma Models.Cancer medicine · 2026Article
- The role of metformin in extracellular matrix-based three-dimensional cell culture Models: A mini-review on therapeutic potentials.Biochemistry and biophysics reports · 2026Review
- Metformin and its derivatives in breast cancer: from glycaemic control to tumor-intrinsic pathways.Breast cancer research : BCR · 2025Review
- Metformin and its Nanoformulations in Cancer Prevention and Therapy.Current pharmaceutical design · 2025Review
- Metformin: A Dual-Role Player in Cancer Treatment and Prevention.International journal of molecular sciences · 2024Review
- Clinical advances in analytical profiling of signature lipids: implications for severe non-communicable and neurodegenerative diseases.Metabolomics : Official journal of the Metabolomic Society · 2024Review
- Impact of De Novo Cholesterol Biosynthesis on the Initiation and Progression of Breast Cancer.Biomolecules · 2024Review
- Intermediate Filaments in Breast Cancer Progression, and Potential Biomarker for Cancer Therapy: A Narrative Review.Breast cancer (Dove Medical Press) · 2024Review
- The impact of lipid metabolism on breast cancer: a review about its role in tumorigenesis and immune escape.Cell communication and signaling : CCS · 2023Review
- Identification of CYP3A4 inhibitors as potential anti-cancer agents using pharmacoinformatics approach.Journal of molecular modeling · 2023Article
- Article
- Nm23-H1 activator phenylbutenoid dimer exerts cytotoxic effects on metastatic breast cancer cells by inducing mitochondrial dysfunction only under glucose starvation.Scientific reports · 2021Article
- Metformin impairs cisplatin resistance effects in A549 lung cancer cells through mTOR signaling and other metabolic pathways.International journal of oncology · 2021Article
- Synthesis and Characterization of Lipophilic Salts of Metformin to Improve Its Repurposing for Cancer Therapy.ACS omega · 2021Article
- Profile of copper-associated DNA methylation and its association with incident acute coronary syndrome.Clinical epigenetics · 2021Article
- Mechanistic Insights Delineating the Role of Cholesterol in Epithelial Mesenchymal Transition and Drug Resistance in Cancer.Frontiers in cell and developmental biology · 2021Review
- Cholesterol-Lowering Drugs on Akt Signaling for Prevention of Tumorigenesis.Frontiers in genetics · 2021Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin, a widely prescribed anti-diabetic drug, shows anticancer activity in various cancer types. Few studies documented that there was a decreased level of LDL and total cholesterol in blood serum of metformin users. Based on these views, this study aimed to determine if metformin exhibits anticancer activity by alleviating cholesterol level in cancer cells. The present study found that treatment of breast cancer MDA-MB-231 cells with metformin significantly decreased cholesterol content with concomitant inhibition of various cholesterol regulatory genes (e.g., HMGCoR, LDLR and SREBP1). Metformin decreased cell viability, migration and stemness in metastatic MDA-MB-231 cells. Similarly, metformin treatment suppressed expressions of anti-apoptotic genes BCL2 and Bcl-xL, and mesenchymal genes vimentin, N-cadherin, Zeb1 and Zeb2 with simultaneous enhancement of apoptotic caspase 3 and Bax, and epithelial genes E-cadherin and keratin 19 expressions, confirming an inhibitory effect of metformin in tumorigenesis. Similar to metformin, depletion of cholesterol by methyl beta cyclodextrin (MBCD) diminished cell viability, migration, EMT and stemness in breast cancer cells. Moreover, metformin-inhibited cell viability, migration, colony and sphere formations were reversed back by cholesterol treatment. Similarly, cholesterol treatment inverted metformin-reduced several gene expressions (e.g., Bcl-xL, BCL2, Zeb1, vimentin, and BMI-1). Additionally, zymography data demonstrated that cholesterol upregulated metformin-suppressed MMP activity. These findings suggested that metformin revealed anticancer activity by lowering of cholesterol content in breast cancer cells. Thus, this study, for the first time, unravelled this additional mechanism of metformin-mediated anticancer activity.
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Registered trials
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