ArticlePloS one2010
Telomere shortening sensitizes cancer cells to selected cytotoxic agents: in vitro and in vivo studies and putative mechanisms.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- Review
- Telomerase inhibitors TMPyP4 and BIBR 1532 show synergistic antitumor activity in combination with chemotherapeutic drugs.Scientific reports · 2025Article
- Obesity-Senescence-Breast Cancer: Clinical Presentation of a Common Unfortunate Cycle.Advances in experimental medicine and biology · 2024Review
- Exosomal telomerase transcripts reprogram the microRNA transcriptome profile of fibroblasts and partially contribute to CAF formation.Scientific reports · 2022Article
- Drug discovery of small molecules targeting the higher-order hTERT promoter G-quadruplex.PloS one · 2022Article
- Review
- Oligonucleotides Targeting Telomeres and Telomerase in Cancer.Molecules (Basel, Switzerland) · 2018Review
- Perspectives on the combination of radiotherapy and targeted therapy with DNA repair inhibitors in the treatment of pancreatic cancer.World journal of gastroenterology · 2016Review
- XRCC3 is a promising target to improve the radiotherapy effect of esophageal squamous cell carcinoma.Cancer science · 2015Article
- Proteomic and microRNA data clarifying the effects of telomere shortening on cancer cells.Data in brief · 2015Article
- Keeping those telomeres short! an innovative intratumoral long-term drug delivery system.Journal of cancer research and clinical oncology · 2015Article
- Telomerase variant A279T induces telomere dysfunction and inhibits non-canonical telomerase activity in esophageal carcinomas.PloS one · 2014Article
- 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
- A yeast chemical genetic screen identifies inhibitors of human telomerase.Chemistry & biology · 2013Article
- Telomere shortening and Alzheimer's disease.Neuromolecular medicine · 2013Review
- Effect of targeted silencing of hTERT mRNA by lentivirus-mediated siRNA on A549 lung cancer cells in vitro.Molecular biology reports · 2013Article
- Differential downregulation of telomerase activity by bortezomib in multiple myeloma cells-multiple regulatory pathways in vitro and ex vivo.British journal of cancer · 2012Article
- Anthracyclines disrupt telomere maintenance by telomerase through inducing PinX1 ubiquitination and degradation.Oncogene · 2012Article
- Article
- The combined use of known antiviral reverse transcriptase inhibitors AZT and DDI induce anticancer effects at low concentrations.Neoplasia (New York, N.Y.) · 2012Article
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTelomere/telomerase system has been recently recognized as an attractive target for anticancer therapy. Telomerase inhibition results in tumor regression and increased sensitivity to various cytotoxic drugs. However, it has not been fully established yet whether the mediator of these effects is telomerase inhibition per se or telomere shortening resulting from inhibition of telomerase activity. In addition, the characteristics and mechanisms of sensitization to cytotoxic drugs caused by telomerase inhibition has not been elucidated in a systematic manner. METHODOLOGY/PRINCIPAL
findingsIn this study we characterized the relative importance of telomerase inhibition versus telomere shortening in cancer cells. Sensitization of cancer cells to cytotoxic drugs was achieved by telomere shortening in a length dependent manner and not by telomerase inhibition per se. In our system this sensitization was related to the mechanism of action of the cytotoxic drug. In addition, telomere shortening affected also other cancer cell functions such as migration. Telomere shortening induced DNA damage whose repair was impaired after administration of cisplatinum while doxorubicin or vincristine did not affect the DNA repair. These findings were verified also in in vivo mouse model. The putative explanation underlying the phenotype induced by telomere shortening may be related to changes in expression of various microRNAs triggered by telomere shortening. CONCLUSIONS/SIGNIFICANCE: To our best knowledge this is the first study characterizing the relative impact of telomerase inhibition and telomere shortening on several aspects of cancer cell phenotype, especially related to sensitivity to cytotoxic drugs and its putative mechanisms. The microRNA changes in cancer cells upon telomere shortening are novel information. These findings may facilitate the development of telomere based approaches in treatment of cancer.
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