ArticleMolecular cancer2005
Telomerase inhibition by siRNA causes senescence and apoptosis in Barrett's adenocarcinoma cells: mechanism and therapeutic potential.
Article in Molecular cancer, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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43 citing papers in PubMed, 93 citations in OpenAlex.
- CRISPRi-Mediated Epigenetic Suppression of TERT Reduces Cell Growth in Non-Small-Cell Lung Cancer Cells.Cells · 2026Article
- Recent progress in human telomerase structure and its therapeutic targeting.Frontiers in molecular biosciences · 2025Review
- Teloxantron inhibits the processivity of telomerase with preferential DNA damage on telomeres.Cell death & disease · 2022Article
- The Role of WRAP53 in Cell Homeostasis and Carcinogenesis Onset.Current issues in molecular biology · 2022Review
- Terpyridine platinum compounds induce telomere dysfunction and chromosome instability in cancer cells.Oncotarget · 2021Article
- Combined treatment with emodin and a telomerase inhibitor induces significant telomere damage/dysfunction and cell death.Cell death & disease · 2019Article
- Stilbene Compounds Inhibit Tumor Growth by the Induction of Cellular Senescence and the Inhibition of Telomerase Activity.International journal of molecular sciences · 2019Review
- Telomerase Deficiency Predisposes to Heart Failure and Ischemia-Reperfusion Injury.Frontiers in cardiovascular medicine · 2019Article
- hTERT gene knockdown enhances response to radio- and chemotherapy in head and neck cancer cell lines through a DNA damage pathway modification.Scientific reports · 2018Article
- CRISPR-Cas9 Mediated Telomere Removal Leads to Mitochondrial Stress and Protein Aggregation.International journal of molecular sciences · 2017Article
- Functional role ofOncotarget · 2017Article
- hTERT-Immortalized Bone Mesenchymal Stromal Cells Expressing Rat Galanin via a Single Tetracycline-Inducible Lentivirus System.Stem cells international · 2017Article
- RNA interference mediated downregulation of human telomerase reverse transcriptase (hTERT) in LN18 cells.Cytotechnology · 2016Article
- Therapeutic targeting of replicative immortality.Seminars in cancer biology · 2015Review
- On the road with WRAP53β: guardian of Cajal bodies and genome integrity.Frontiers in genetics · 2015Review
- Effects of epigallocatechin gallate on the proliferation and apoptosis of the nasopharyngeal carcinoma cell line CNE2.Experimental and therapeutic medicine · 2014Article
- Article
- Biology of telomeres: importance in etiology of esophageal cancer and as therapeutic target.Translational research : the journal of laboratory and clinical medicine · 2013Review
- Telomerase downregulation induces proapoptotic genes expression and initializes breast cancer cells apoptosis followed by DNA fragmentation in a cell type dependent manner.Molecular biology reports · 2013Article
- Telomerase as a useful target in cancer fighting-the breast cancer case.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2013Review
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7 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundIn cancer cells, telomerase induction helps maintain telomere length and thereby bypasses senescence and provides enhanced replicative potential. Chemical inhibitors of telomerase have been shown to reactivate telomere shortening and cause replicative senescence and apoptotic cell death of tumor cells while having little or no effect on normal diploid cells.
resultsWe designed siRNAs against two different regions of telomerase gene and evaluated their effect on telomere length, proliferative potential, and gene expression in Barrett's adenocarcinoma SEG-1 cells. The mixture of siRNAs in nanomolar concentrations caused a loss of telomerase activity that appeared as early as day 1 and was essentially complete at day 3. Inhibition of telomerase activity was associated with marked reduction in median telomere length and complete loss of detectable telomeres in more than 50% of the treated cells. Telomere loss caused senescence in 40% and apoptosis in 86% of the treated cells. These responses appeared to be associated with activation of DNA sensor HR23B and subsequent activation of p53 homolog p73 and p63 and E2F1. Changes in these gene regulators were probably the source of observed up-regulation of cell cycle inhibitors, p16 and GADD45. Elevated transcript levels of FasL, Fas and caspase 8 that activate death receptors and CARD 9 that interacts with Bcl10 and NFKB to enhance mitochondrial translocation and activation of caspase 9 were also observed.
conclusionThese studies show that telomerase siRNAs can cause effective suppression of telomerase and telomere shortening leading to both cell cycle arrest and apoptosis via mechanisms that include up-regulation of several genes involved in cell cycle arrest and apoptosis. Telomerase siRNAs may therefore be strong candidates for highly selective therapy for chemoprevention and treatment of Barrett's adenocarcinoma.
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