{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:48:46Z","timestamp":1791953326077,"version":"4.3.4"},"reference-count":33,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008693","name":"Gulf Medical University","doi-asserted-by":"publisher","award":["IRB-COM-STD-162-JUNE-2024"],"award-info":[{"award-number":["IRB-COM-STD-162-JUNE-2024"]}],"id":[{"id":"10.13039\/100008693","id-type":"DOI","asserted-by":"publisher"}]},{"award":["IRB-COM-STD-162-JUNE-2024"],"award-info":[{"award-number":["IRB-COM-STD-162-JUNE-2024"]}],"id":[{"id":"https:\/\/ror.org\/02kaerj47","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Waterpipe (shisha or hookah) smoking is recognized as a risk factor for lung cancer; however, its interference with hypoxia stress and tumor suppressor pathways in non-small cell lung cancer (NSCLC) is poorly defined. In this study, NSCLC cell lines (A549, H460, H226 with endogenous wild-type p53, and H1299 transiently expressing wild-type or p53 mutants) were exposed to waterpipe smoke condensate (WPSC) under normoxic and\/or hypoxic conditions. WPSC induced HIF-1\u03b1 stabilization under normoxic conditions, accompanied by predominantly cytoplasmic localization and without corresponding induction of the canonical HIF-1 target genes examined. In parallel, WPSC transiently reduced nuclear p53 localization without altering total p53 protein levels. In A549 cells, WPSC pretreatment attenuated irradiation-induced expression of the p53 target genes cyclin-dependent kinase inhibitor 1A (CDKN1A) and BTG anti-proliferation factor 2 (BTG2). Pharmacological inhibition of HIF-1\u03b1 partially restored nuclear p53 localization, supporting the involvement of HIF-1\u03b1 in this response. Co-immunoprecipitation demonstrated an association between HIF-1\u03b1 and p53 following WPSC exposure. Collectively, these findings show that WPSC-induced HIF-1\u03b1 stabilization under normoxic conditions is associated with transient alterations in p53 localization and transcriptional response, supporting an involvement of HIF-1\u03b1 in this process.<\/jats:p>","DOI":"10.3390\/ijms27198927","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:40:17Z","timestamp":1791596417000},"page":"8927","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Waterpipe Smoke Condensate Impairs p53 Nuclear Localization in Association with HIF-1\u03b1 Stabilization"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7195-5101","authenticated-orcid":false,"given":"Husam","family":"Nawafleh","sequence":"first","affiliation":[{"name":"Thumbay Research Institute for Precision Medicine, Gulf Medical University, Al Jurf 1, Ajman P.O. Box 4184, United Arab Emirates"},{"name":"College of Medicine, Gulf Medical University, Al Jurf 1, Ajman P.O. Box 4184, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0998-3627","authenticated-orcid":false,"given":"Jerome","family":"Thiery","sequence":"additional","affiliation":[{"name":"INSERM UMR 1356, Next-Generation Immuno-Oncology Research and Therapy in Pediatric and Adult Cancer, Gustave Roussy, Faculty of Medicine, Universit\u00e9 Paris-Saclay, 114 Rue \u00c9douard-Vaillant, 94805 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yehya","family":"Elsayed","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abderemane","family":"Abdou","sequence":"additional","affiliation":[{"name":"INSERM UMR 1356, Next-Generation Immuno-Oncology Research and Therapy in Pediatric and Adult Cancer, Gustave Roussy, Faculty of Medicine, Universit\u00e9 Paris-Saclay, 114 Rue \u00c9douard-Vaillant, 94805 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salem","family":"Chouaib","sequence":"additional","affiliation":[{"name":"Thumbay Research Institute for Precision Medicine, Gulf Medical University, Al Jurf 1, Ajman P.O. Box 4184, United Arab Emirates"},{"name":"INSERM UMR 1356, Next-Generation Immuno-Oncology Research and Therapy in Pediatric and Adult Cancer, Gustave Roussy, Faculty of Medicine, Universit\u00e9 Paris-Saclay, 114 Rue \u00c9douard-Vaillant, 94805 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9132-5940","authenticated-orcid":false,"given":"Rania F.","family":"Zaarour","sequence":"additional","affiliation":[{"name":"Thumbay Research Institute for Precision Medicine, Gulf Medical University, Al Jurf 1, Ajman P.O. Box 4184, United Arab Emirates"},{"name":"College of Medicine, Gulf Medical University, Al Jurf 1, Ajman P.O. Box 4184, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"ref_1","first-page":"45","article-title":"Epidemiology of lung cancer","volume":"25","author":"Thandra","year":"2021","journal-title":"Contemp. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2838","DOI":"10.1158\/0008-5472.CAN-24-3525","article-title":"Tobacco Smoking Rewires Cell Metabolism by Inducing GAPDH Succinylation to Promote Lung Cancer Progression","volume":"85","author":"Wang","year":"2025","journal-title":"Cancer Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1183\/16000617.0374-2020","article-title":"Waterpipe smoking: A review of pulmonary and health effects","volume":"30","author":"Darawshy","year":"2021","journal-title":"Eur. Respir. 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