ArticlePloS one2015
Doxycycline Induces Apoptosis and Inhibits Proliferation and Invasion of Human Cervical Carcinoma Stem Cells.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- Repurposing Non-oncologic Drugs via Targeted Nanocarriers for Cancer Therapy: Mechanisms, Synergistic Combinations, and Clinical Translation.AAPS PharmSciTech · 2026Review
- Enhanced targeted treatment of cervical cancer using nanoparticle-based doxycycline delivery system.Scientific reports · 2025Article
- Doxycycline Restores Gemcitabine Sensitivity in Preclinical Models of Multidrug-Resistant Intrahepatic Cholangiocarcinoma.Cancers · 2025Article
- Mitochondrial ribosomal proteins: potential targets for cancer prognosis and therapy.Frontiers in oncology · 2025Review
- Targeting Cervical Cancer Stem Cells by Phytochemicals.Current medicinal chemistry · 2024Review
- Metabolic vulnerability of cancer stem cells and their niche.Frontiers in pharmacology · 2024Review
- Repurposing approved non-oncology drugs for cancer therapy: a comprehensive review of mechanisms, efficacy, and clinical prospects.European journal of medical research · 2023Review
- Unveiling diagnostic and therapeutic strategies for cervical cancer: biomarker discovery through proteomics approaches and exploring the role of cervical cancer stem cells.Frontiers in oncology · 2023Review
- Role of Integrin αvβ3 in Doxycycline-Induced Anti-Proliferation in Breast Cancer Cells.Frontiers in cell and developmental biology · 2022Article
- Doxycycline Significantly Enhances Induction of Induced Pluripotent Stem Cells to Endoderm by Enhancing Survival Through Protein Kinase B Phosphorylation.Hepatology (Baltimore, Md.) · 2021Article
- Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives.Biomolecules · 2020Review
- ALDH-1-positive cells exhibited a radioresistant phenotype that was enhanced with hypoxia in cervical cancer.BMC cancer · 2020Article
- Mitochondrial cross-compartmental signalling to maintain proteostasis and longevity.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2020Review
- Targeted Gene Delivery Therapies for Cervical Cancer.Cancers · 2020Review
- Crosstalk between autophagy and metabolic regulation of cancer stem cells.Molecular cancer · 2020Review
- Cervical cancer stem cells and other leading factors associated with cervical cancer development.Oncology letters · 2019Review
- Zoledronic acid inhibits the growth of cancer stem cell derived from cervical cancer cell by attenuating their stemness phenotype and inducing apoptosis and cell cycle arrest through the Erk1/2 and Akt pathways.Journal of experimental & clinical cancer research : CR · 2019Article
- Metabolism-Based Therapeutic Strategies Targeting Cancer Stem Cells.Frontiers in pharmacology · 2019Review
- CD4+ memory T cells infected with latent HIV-1 are susceptible to drugs targeting telomeres.Cell cycle (Georgetown, Tex.) · 2018Article
- Induction of Mitochondrial Dysfunction and Oxidative Damage by Antibiotic Drug Doxycycline Enhances the Responsiveness of Glioblastoma to Chemotherapy.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCancer stem cells (CSCs) are proposed to be responsible for high recurrence rate in cervical carcinoma. Reagents that can suppress the proliferation and differentiation of CSCs would provide new opportunities to fight against tumor recurrence. Doxycycline has been reported as a potential anti-cancer compound. However, few studies investigated its inhibitory effect against cervical cancer stem cells.
methodsHeLa cells were cultured in cancer stem cell conditional media in a poly-hema-treated dish. In this non-adhesive culture system, HeLa cells were treated with cisplatin until some cells survived and formed spheroids, which were then collected and injected into the immunodeficient mice. Cisplatin was administered every three days for five times. The tumor xenografts with CSC enrichment were cultured in cancer stem cell specific medium again to form tumorsphere, which we called HeLa-CSCs. Expression of cancer stem cell markers in HeLa-CSCs was measured by flow cytometry and qPCR. HeLa-CSCs were then treated with doxycycline. Proliferation and differentiation rates were determined by the size of spheres formed in vitro and tumor formed in vivo.
resultsWe developed a new strategy to selectively enrich CSCs from human cervical carcinoma cell line HeLa, and these HeLa-CSCs are CD133+/CD49f+ cell populations with significantly enhanced expression of stem cell markers. When these HeLa-CSCs were treated with doxycycline, the colony formation, proliferation, migration and invasion, and differentiation were all suppressed. Meanwhile, stem cell markers SOX-2, OCT-4, NANOG, NOTCH and BMI-1 decreased in doxycycline treated cells, so as the surface markers CD133 and CD49f. Furthermore, proliferation markers Ki67 and PCNA were also decreased by doxycycline treatment in the in vivo xenograft mouse model.
conclusionsCancer stem cells are enriched from sphere-forming and chemoresistant HeLa-derived tumor xenografts in immunodeficient mice. Doxycycline inhibits proliferation, invasion, and differentiation, and also induces apoptosis of these HeLa-CSCs in vitro and in vivo.
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