ArticleOncotarget2016
Lactoferrin selectively triggers apoptosis in highly metastatic breast cancer cells through inhibition of plasmalemmal V-H+-ATPase.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 50 citations in OpenAlex.
- Lactoferrin and Nanotechnology: New Insights Into Glioblastoma Therapy.CNS neuroscience & therapeutics · 2026Review
- Whey Processed Oxymel induces apoptosis and S-phase arrest in MCF7 and MDA-MB-468 breast cancer cells.Scientific reports · 2026Article
- Lactoferrin as a Non-Hormonal Therapeutic Candidate for Endometriosis: Mechanisms and Future Directions.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- Breast Cancer in Relation to Dairy Product Consumption: A Review of Current Findings and Potential Mechanisms.Current nutrition reports · 2026Review
- Anticancer potential of lactoferrin: effects, drug synergy and molecular interactions.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025Review
- V-ATPase in cancer: mechanistic insights and therapeutic potentials.Cell communication and signaling : CCS · 2024Review
- Double-Edged Sword Effect of Diet and Nutrition on Carcinogenic Molecular Pathways in Breast Cancer.International journal of molecular sciences · 2024Review
- Nutraceutical and Health-Promoting Potential of Lactoferrin, an Iron-Binding Protein in Human and Animal: Current Knowledge.Biological trace element research · 2024Review
- Therapeutic potential of lactoferrin-coated iron oxide nanospheres for targeted hyperthermia in gastric cancer.Scientific reports · 2023Article
- Antitumor activity of bovine lactoferrin and its derived peptides against HepG2 liver cancer cells and Jurkat leukemia cells.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2023Article
- Inhibition of DAMP actions in the tumoral microenvironment using lactoferrin-glycyrrhizin conjugate for glioblastoma therapy.Biomaterials research · 2023Article
- Targeted Fisetin-Encapsulated β-Cyclodextrin Nanosponges for Breast Cancer.Pharmaceutics · 2023Article
- Lactoferrin as a Human Genome "Guardian"-An Overall Point of View.International journal of molecular sciences · 2022Review
- Plasmalemmal V-ATPase as a Potential Biomarker for Lactoferrin-Based Anticancer Therapy.Biomolecules · 2022Article
- Article
- A Novel Human Recombinant Lactoferrin Inhibits Lung Adenocarcinoma Cell Growth and Migration with No Cytotoxic Effect on Normal Human Epithelial Cells.Archivum immunologiae et therapiae experimentalis · 2021Article
- Surface-Tailored Zein Nanoparticles: Strategies and Applications.Pharmaceutics · 2021Review
- Recombinant human lactoferrin carrying humanized glycosylation exhibits antileukemia selective cytotoxicity, microfilament disruption, cell cycle arrest, and apoptosis activities.Investigational new drugs · 2021Article
- Lactoferrin: A Glycoprotein Involved in Immunomodulation, Anticancer, and Antimicrobial Processes.Molecules (Basel, Switzerland) · 2021Review
- Lactoferrin, a multi-functional glycoprotein: Active therapeutic, drug nanocarrier & targeting ligand.Biomaterials · 2020Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Breast cancer is the most common type of cancer affecting women. Despite the good prognosis when detected early, significant challenges remain in the treatment of metastatic breast cancer. The recruitment of the vacuolar H+-ATPase (V-H+-ATPase) to the plasma membrane, where it mediates the acidification of the tumor microenvironment (TME), is a recognized feature involved in the acquisition of a metastatic phenotype in breast cancer. Therefore, inhibitors of this pump have emerged as promising anticancer drugs. Lactoferrin (Lf) is a natural pro-apoptotic iron-binding glycoprotein with strong anticancer activity whose mechanism of action is not fully understood. Here, we show that bovine Lf (bLf) preferentially induces apoptosis in the highly metastatic breast cancer cell lines Hs 578T and MDA-MB-231, which display a prominent localisation of V-H+-ATPase at the plasma membrane, but not in the lowly metastatic T-47D or in the non-tumorigenic MCF-10-2A cell lines. We also demonstrate that bLf decreases the extracellular acidification rate and causes intracellular acidification in metastatic breast cancer cells and, much like the well-known proton pump inhibitors concanamycin A and bafilomycin A1, inhibits V-H+-ATPase in sub-cellular fractions. These data further support that bLf targets V-H+-ATPase and explain the selectivity of bLf for cancer cells, especially for highly metastatic breast cancer cells. Altogether, our results pave the way for more rational in vivo studies aiming to explore this natural non-toxic compound for metastatic breast cancer therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.