{
  "abstract": "Waterpipe smoking has emerged as a major global health concern, with incompletely characterized effects on bronchial epithelial cells. In this study, we investigated the cytotoxic and adaptive responses of non-tumorigenic human bronchial epithelial BEAS-2B cells exposed to waterpipe smoke condensate (WPSC). Increasing concentrations of WPSC reduced cell viability in a dose-dependent manner; however, exposure to 0.1% WPSC caused only a modest, transient reduction in viability that was no longer significant by 72 hrs and did not significantly induce apoptosis over 72 hrs, as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and Annexin V/Propidium Iodide (PI) apoptosis assays. To elucidate the adaptive mechanisms underlying this resistance, we examined autophagic flux and found that WPSC induced time-dependent accumulation of LC3-II and p62, which was enhanced by bafilomycin A1 cotreatment, indicating the activation of autophagy. This was accompanied by increased phosphorylation of AMPK and decreased phosphorylation of mTORC1, consistent with an autophagy-mediated stress response. Functionally, the inhibition of autophagy with bafilomycin A1 increased apoptosis and necrosis, suggesting that autophagy could play a protective role. Moreover, WPSC exposure induced DNA damage, as evidenced by increased γH2AX and 53BP1 nuclear foci, and elevated proinflammatory cytokine expression (IL-1β and CCL2). Finally, WPSC treatment upregulated the expression of the cancer stem cell-associated markers CD44 and CD133. Collectively, our findings demonstrate that subcytotoxic exposure to waterpipe smoke activates autophagy in non-tumorigenic lung epithelial cells. This adaptive mechanism may represent an early cellular event linking waterpipe smoke exposure to lung carcinogenesis.",
  "abstract_shown": true,
  "affiliations": [
    "Thumbay Research Institute for Precision Medicine, Gulf Medical University, Ajman, United Arab Emirates",
    "Molecular and Translational Medicine Laboratory, Faculty of Medicine, Beirut Arab University, Beirut, Lebanon",
    "Department Chemistry, Wayne State University, Detroit, United States of America",
    "INSERM UMR 1356, Next-Generation Immuno-Oncology Research and Therapy in Pediatric and Adult Cancer, Gustave Roussy, Faculty of Medicine, University Paris-Saclay, Villejuif, France"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Rania F. Zaarour"
    },
    {
      "affs": [
        1
      ],
      "name": "Bilal Azakir"
    },
    {
      "affs": [
        2
      ],
      "name": "Ayda S. Mahmood"
    },
    {
      "affs": [
        3
      ],
      "name": "Zohra Nizami"
    },
    {
      "name": "Husam Nawafleh"
    },
    {
      "name": "Yehya ElSayed"
    },
    {
      "name": "Salem Chouaib"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3wsdbx8htt8e0.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0358943",
  "fulltext_url": null,
  "id": "3wsdbx8htt8e0",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0358943",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2713|Autophagy in Disease and Therapy"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Nucleic acids/DNA/DNA damage"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cell processes/Cell death/Apoptosis"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cell processes/Cell death/Autophagic cell death"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Signal transduction/Cell signaling"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/DNA/DNA damage"
    ],
    [
      "plos",
      "/Biology and life sciences/Immunology/Immune response/Inflammation"
    ],
    [
      "plos",
      "/Biology and life sciences/Psychology/Behavior/Habits/Smoking habits"
    ],
    [
      "plos",
      "/Medicine and health sciences/Clinical medicine/Signs and symptoms/Inflammation"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune response/Inflammation"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancer treatment"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms/Lung and intrathoracic tumors"
    ],
    [
      "plos",
      "/Social sciences/Psychology/Behavior/Habits/Smoking habits"
    ]
  ],
  "openalex": "W7213274075",
  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0358943&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-24",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/3wsdbx8htt8e0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:43Z",
      "native_id": "10.1371/journal.pone.0358943",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0358943"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
    },
    {
      "field": "biology",
      "origin": "plos:immunology",
      "subfield": "immunology"
    },
    {
      "field": "medicine",
      "origin": "plos:oncology",
      "subfield": "oncology"
    }
  ],
  "title": "Waterpipe smoke condensate activates autophagy in non-tumorigenic lung epithelial cells: Implications for inflammation and stemness",
  "title_text": "Waterpipe smoke condensate activates autophagy in non-tumorigenic lung epithelial cells: Implications for inflammation and stemness",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:43Z",
  "url": "https://research.draconitic.com/paper/3wsdbx8htt8e0",
  "venue": "PLOS One",
  "versions": []
}