Waterpipe Smoke Condensate Impairs p53 Nuclear Localization in Association with HIF-1α Stabilization
4 affiliations
- 1Thumbay Research Institute for Precision Medicine, Gulf Medical University, Al Jurf 1, Ajman P.O. Box 4184, United Arab Emirates
- 2College of Medicine, Gulf Medical University, Al Jurf 1, Ajman P.O. Box 4184, United Arab Emirates
- 3INSERM UMR 1356, Next-Generation Immuno-Oncology Research and Therapy in Pediatric and Adult Cancer, Gustave Roussy, Faculty of Medicine, Université Paris-Saclay, 114 Rue Édouard-Vaillant, 94805 Villejuif, France
- 4Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, MI 48202, USA
Abstract
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-1α 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-1α partially restored nuclear p53 localization, supporting the involvement of HIF-1α in this response. Co-immunoprecipitation demonstrated an association between HIF-1α and p53 following WPSC exposure. Collectively, these findings show that WPSC-induced HIF-1α stabilization under normoxic conditions is associated with transient alterations in p53 localization and transcriptional response, supporting an involvement of HIF-1α in this process.
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BibTeX
@article{nawafleh2026waterpipe,
title = {{Waterpipe Smoke Condensate Impairs p53 Nuclear Localization in Association with HIF-1α Stabilization}},
author = {Husam Nawafleh and Jerome Thiery and Yehya Elsayed and Abderemane Abdou and Salem Chouaib and Rania F. Zaarour},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27198927},
url = {https://www.mdpi.com/1422-0067/27/19/8927},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Waterpipe Smoke Condensate Impairs p53 Nuclear Localization in Association with HIF-1α Stabilization
AU - Husam Nawafleh
AU - Jerome Thiery
AU - Yehya Elsayed
AU - Abderemane Abdou
AU - Salem Chouaib
AU - Rania F. Zaarour
PY - 2026
DA - 2026/10/08
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27198927
UR - https://www.mdpi.com/1422-0067/27/19/8927
AB - 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-1α 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-1α partially restored nuclear p53 localization, supporting the involvement of HIF-1α in this response. Co-immunoprecipitation demonstrated an association between HIF-1α and p53 following WPSC exposure. Collectively, these findings show that WPSC-induced HIF-1α stabilization under normoxic conditions is associated with transient alterations in p53 localization and transcriptional response, supporting an involvement of HIF-1α in this process.
SN - 1422-0067
ER -