ArticleAging2019
Doxycycline, Azithromycin and Vitamin C (DAV): A potent combination therapy for targeting mitochondria and eradicating cancer stem cells (CSCs).
Article in Aging, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 78 citations in OpenAlex.
- Cancer Therapy Using Antiparasitic Medications Guided by Acupuncture Meridian Assessment: A Case Series of Six Patients.Integrative medicine (Encinitas, Calif.) · 2026Article
- Review
- Overcoming resistance in lung cancer: combined mitochondrial destabilization by lipophilic cations and doxycycline in hypoxic non-small cell lung carcinoma.Frontiers in pharmacology · 2026Article
- Complete Regression of 11 Hepatic Metastases in Metastatic Pancreatic Adenosquamous Carcinoma and the Role of GPT in Patient Navigation.International medical case reports journal · 2026Article
- Mitochondrial DNA Mutations in Colorectal Cancer Stem Cells: Implications for Tumor Dynamics and Therapeutic Strategies.Current medicinal chemistry · 2026Review
- High-dose vitamin C as a metabolic treatment of cancer: a new dimension in the era of adjuvant and intensive therapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Organelle-tuning condition robustly fabricates energetic mitochondria for cartilage regeneration.Bone research · 2025Article
- Targeting mitochondrial function as a potential therapeutic approach for allergic asthma.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Prokaryotic organelle mitochondria drive tumorigenesis: "the original sin".Frontiers in oncology · 2025Review
- Review
- Azithromycin reduces hemoglobin-induced innate neuroimmune activation.Experimental neurology · 2024Article
- Metabolic vulnerability of cancer stem cells and their niche.Frontiers in pharmacology · 2024Review
- Vitamin C, doxycycline, and azithromycin (VDA) targeted changes in cellular senescence-related genes in human adipose-derived mesenchymal stem cells.Iranian journal of basic medical sciences · 2024Article
- Article
- Article
- Azithromycin inhibits glioblastoma angiogenesis in mice via inducing mitochondrial dysfunction and oxidative stress.Cancer chemotherapy and pharmacology · 2023Article
- Natural Mitochondria Targeting Substances and Their Effect on Cellular Antioxidant System as a Potential Benefit in Mitochondrial Medicine for Prevention and Remediation of Mitochondrial Dysfunctions.Current issues in molecular biology · 2023Review
- Genetic heterogeneity of colorectal cancer and the microbiome.World journal of gastrointestinal oncology · 2023Review
- Unraveling the Peculiar Features of Mitochondrial Metabolism and Dynamics in Prostate Cancer.Cancers · 2023Review
- Pharmacological vitamin C inhibits mTOR signaling and tumor growth by degrading Rictor and inducing HMOX1 expression.PLoS genetics · 2023Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Here, we devised a new strategy for eradicating cancer stem cells (CSCs), via a "synthetic-metabolic" approach, involving two FDA-approved antibiotics and a dietary vitamin supplement. This approach was designed to induce a "rho-zero-like" phenotype in cancer cells. This strategy effectively results in the synergistic eradication of CSCs, using vanishingly small quantities of two antibiotics. The 2 metabolic targets are i) the large mitochondrial ribosome and ii) the small mitochondrial ribosome. Azithromycin inhibits the large mitochondrial ribosome as an off-target side-effect. In addition, Doxycycline inhibits the small mitochondrial ribosome as an off-target side-effect. Vitamin C acts as a mild pro-oxidant, which can produce free radicals and, as a consequence, induces mitochondrial biogenesis. Remarkably, treatment with a combination of Doxycycline (1 μM), Azithromycin (1 μM) plus Vitamin C (250 μM) very potently inhibited CSC propagation by >90%, using the MCF7 ER(+) breast cancer cell line as a model system. The strong inhibitory effects of this DAV triple combination therapy on mitochondrial oxygen consumption and ATP production were directly validated using metabolic flux analysis. Therefore, the induction of mitochondrial biogenesis due to mild oxidative stress, coupled with inhibition of mitochondrial protein translation, may be a new promising therapeutic anti-cancer strategy. Consistent with these assertions, Vitamin C is known to be highly concentrated within mitochondria, by a specific transporter, namely SVCT2, in a sodium-coupled manner. Also, the concentrations of antibiotics used here represent sub-antimicrobial levels of Doxycycline and Azithromycin, thereby avoiding the potential problems associated with antibiotic resistance. Finally, we also discuss possible implications for improving health-span and life-span, as Azithromycin is an anti-aging drug that behaves as a senolytic, which selectively kills and removes senescent fibroblasts.
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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.