{"doi":"10.1038/cddis.2017.333","title":"P53-dependent downregulation of hTERT protein expression and telomerase activity induces senescence in lung cancer cells as a result of pterostilbene treatment","abstract":"<jats:title>Abstract</jats:title><jats:p>Cellular senescence is characterized by permanent cell cycle arrest, triggered by a variety of stresses, such as telomerase inhibition, and it is recognized as a tumor-suppressor mechanism. In recent years, telomerase has become an important therapeutic target in several cancers; inhibition of telomerase can induce senescence via the DNA damage response (DDR). Pterostilbene (PT), a dimethyl ether analog of resveratrol, possesses a variety of biological functions, including anticancer effects; however, the molecular mechanisms underlying these effects are not fully understood. In this study, we investigated the possible mechanisms of PT-induced senescence through telomerase inhibition in human non-small cell lung cancer cells and delineated the role of p53 in senescence. The results indicated that PT-induced senescence is characterized by a flattened morphology, positive staining for senescence-associated-<jats:italic>β</jats:italic> galactosidase activity, and the formation of senescence-associated heterochromatic foci. Telomerase activity and protein expression was significantly decreased in H460 (p53 wild type) cells compared with H1299 (p53 null) cells and p53 knockdown H460 cells (H460-p53-). A more detailed mechanistic study revealed that PT-induced senescence partially occurred via a p53-dependent mechanism, triggering inhibition of telomerase activity and protein expression, and leading to the DDR, S phase arrest and, finally, cellular senescence. This study is the first to explore the novel anticancer mechanism of PT senescence induction via the inhibition of telomerase in lung cancer cells.</jats:p>","journal":"Cell Death &amp; Disease","year":2017,"id":650199,"datarank":0.637274286307404,"base_score":4.248495242049359,"endowment":4.248495242049359,"self_citation_contribution":0.637274286307404,"citation_network_contribution":0.0,"self_endowment_contribution":0.637274286307404,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":69,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":255951,"name":"Pei-Hsuan Wu","orcid":"0000-0002-6690-0744","position":1,"is_corresponding":false},{"id":125619,"name":"Chi-Tang Ho","orcid":null,"position":2,"is_corresponding":false},{"id":1695270,"name":"Tzong-Der Way","orcid":null,"position":3,"is_corresponding":false},{"id":1695272,"name":"Min-Hsiung Pan","orcid":null,"position":4,"is_corresponding":false},{"id":1695275,"name":"Hsiu-Min Chen","orcid":null,"position":5,"is_corresponding":false},{"id":1695277,"name":"Yuan-Soon Ho","orcid":null,"position":6,"is_corresponding":false},{"id":1695278,"name":"Ying-Jan Wang","orcid":"0000-0003-3169-2495","position":7,"is_corresponding":false},{"id":1695260,"name":"Rong-Jane Chen","orcid":"0000-0002-2326-934X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"P53-dependent downregulation of hTERT protein expression and telomerase activity induces senescence in lung cancer cells as a result of pterostilbene treatment","abstract":"<jats:title>Abstract</jats:title><jats:p>Cellular senescence is characterized by permanent cell cycle arrest, triggered by a variety of stresses, such as telomerase inhibition, and it is recognized as a tumor-suppressor mechanism. In recent years, telomerase has become an important therapeutic target in several cancers; inhibition of telomerase can induce senescence via the DNA damage response (DDR). Pterostilbene (PT), a dimethyl ether analog of resveratrol, possesses a variety of biological functions, including anticancer effects; however, the molecular mechanisms underlying these effects are not fully understood. In this study, we investigated the possible mechanisms of PT-induced senescence through telomerase inhibition in human non-small cell lung cancer cells and delineated the role of p53 in senescence. The results indicated that PT-induced senescence is characterized by a flattened morphology, positive staining for senescence-associated-<jats:italic>β</jats:italic> galactosidase activity, and the formation of senescence-associated heterochromatic foci. Telomerase activity and protein expression was significantly decreased in H460 (p53 wild type) cells compared with H1299 (p53 null) cells and p53 knockdown H460 cells (H460-p53-). A more detailed mechanistic study revealed that PT-induced senescence partially occurred via a p53-dependent mechanism, triggering inhibition of telomerase activity and protein expression, and leading to the DDR, S phase arrest and, finally, cellular senescence. This study is the first to explore the novel anticancer mechanism of PT senescence induction via the inhibition of telomerase in lung cancer cells.</jats:p>","is_dataset_classified":null,"base_score":4.248495242049359,"endowment":4.248495242049359,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28796247","pmcid":"PMC5596539","openalex_id":"https://openalex.org/W2744764618","authors":[],"funders":[],"total_grants":0,"fwci":4.1875,"citation_percentile":0.94873795,"influential_citations":1,"citation_trend":[{"year":2017,"count":2},{"year":2018,"count":5},{"year":2019,"count":9},{"year":2020,"count":13},{"year":2021,"count":10},{"year":2022,"count":12},{"year":2023,"count":8},{"year":2024,"count":4},{"year":2025,"count":5},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.nature.com/articles/cddis2017333.pdf","host_type":"journal"},{"url":"https://www.nature.com/articles/cddis2017333.pdf","host_type":"GOLD"},{"url":"https://www.nature.com/articles/cddis2017333.pdf","host_type":"publisher"},{"url":"https://www.nature.com/articles/cddis2017333","host_type":"publisher"},{"url":"http://www.nature.com/doifinder/10.1038/cddis.2017.333","host_type":"publisher"},{"url":"https://doi.org/10.1038/cddis.2017.333","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/28796247","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5596539","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC5596539","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC5596539?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Telomeres, Telomerase, and Senescence","Advanced biosensing and bioanalysis techniques","MicroRNA in disease regulation","Medicine","Biology"],"mesh_terms":["Carcinoma, Non-Small-Cell Lung","Fluorescent Antibody Technique","Humans","Lung Neoplasms","Stilbenes","Blotting, Western","Tumor Suppressor Protein p53","Cellular Senescence","Telomerase","Comet Assay","Cell Line, Tumor"],"keywords":["Telomerase","Senescence","Telomerase reverse transcriptase","Telomere","Pterostilbene","Biology","Cell biology","Gene knockdown","Cell cycle","Cell cycle checkpoint","Downregulation and upregulation","Cancer research","DNA damage","Cancer cell","Cell","Cancer","Cell culture","Resveratrol","Biochemistry","Genetics","DNA","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T05:03:09.472989Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}