Hypoxia-drives reversible cell cycle arrest in lung cancer cells via modulation of cellular redox and gene expression.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41023503", "kind": "science-record", "revision": 2, "content_hash": "sha256:80c5b6d7766e62f5ff31faa173f1abcab190d758aeccfe0220bf5b394a8461d8", "created_at": "2026-11-01T20:31:05Z", "updated_at": "2026-11-01T21:35:49Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Hypoxia-drives reversible cell cycle arrest in lung cancer cells via modulation of cellular redox and gene expression.", "doi": "10.1007/s12032-025-03058-9", "pmid": "41023503", "authors": ["Dharmendra Kumar Maurya", "Varshita Mehta", "Babita Singh"], "journal": "Medical oncology (Northwood, London, England)", "year": 2025, "abstract": "Hypoxia is a well-recognized clinical feature of solid tumors, including lung cancer, and is associated with poor prognosis due to its role in promoting resistance to chemotherapy and radiotherapy. To investigate the cellular consequences of hypoxia, we cultured A549 lung adenocarcinoma cells under 1% O2 and examined their growth, cell cycle distribution, and redox status. Hypoxia significantly reduces cell proliferation and induced G1 phase cell cycle arrest, suggesting a cytostatic effect. Biochemical analysis showed a 2.64- and 2.04-fold increase in total and mitochondrial reactive oxygen species (ROS) levels, respectively, along with an elevated total thiol levels under hypoxic conditions compared to normoxia. To assess the reversibility of the hypoxic response, we performed a reciprocal oxygen exposure experiment where cells initially grown under hypoxia were re-exposed to normoxia, and vice versa. To explore the underlying molecular mechanism, we analyzed transcriptomic datasets (GEO accession: GSE48134 and GSE42416) which revealed that hypoxia downregulated key genes involved in energy metabolism (e.g., PDK4, G6PD), cell cycle progression (e.g., CCND1, CDK2), and redox regulation (e.g., GCLM, TXNRD1, NQO1, GCLC). Further, few of redox-related genes were validated by RT-PCR in A549 cells cultured under hypoxia and normoxia for 24 h. Importantly, cyclic hypoxia (intermittent hypoxia-reoxygenation) conditions showed partial restoration of some of these transcripts, supporting the transient nature of hypoxic stress, consistent with our in vitro observations. Furthermore, transcriptome profiles from adenocarcinoma patients (GEO accession: GSE30979) also match our cell line observations. Thus, our results clearly show that hypoxia causes a temporary cell cycle arrest in lung cancer cells, which is reversible when oxygen is restored.", "claims": [{"id": "claim-method", "statement": "The data obtained from the cell viability and cell proliferation assays, the cell cycle, redox status apoptosis assay, and the cell proliferation assay were analyzed using multiple comparison analysis followed by Tukey’s post-hoc test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41023503", "locator": "sections[11] \"Statistical analysis\" paragraph 2", "quote": "The data obtained from the cell viability and cell proliferation assays, the cell cycle, redox status apoptosis assay, and the cell proliferation assay were analyzed using multiple comparison analysis followed by Tukey’s post-hoc test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "No datasets were generated or analysed during the current study.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41023503", "locator": "sections[25] \"Data availability\" paragraph 2", "quote": "No datasets were generated or analysed during the current study."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Thus, our results clearly show that hypoxia causes a temporary cell cycle arrest in lung cancer cells, which is reversible when oxygen is restored.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41023503", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Thus, our results clearly show that hypoxia causes a temporary cell cycle arrest in lung cancer cells, which is reversible when oxygen is restored."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Thus, our results clearly show that hypoxia causes a temporary cell cycle arrest in lung cancer cells, which is reversible when oxygen is restored.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:41023503"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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