ArticleAmerican journal of respiratory cell and molecular biology2009
Nicotine induces resistance to chemotherapy by modulating mitochondrial signaling in lung cancer.
Article in American journal of respiratory cell and molecular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 104 citations in OpenAlex.
- Integrating tobacco treatment into cancer care: Study protocol for a randomized controlled comparative effectiveness trial.Contemporary clinical trials · 2016Trial
- Effect of electronic cigarette aerosols on cisplatin resistance in head and neck cancer cells: a collaborative replication study.BMC cancer · 2026Article
- Prehabilitation Targets Associated with the Omission of Adjuvant Chemotherapy After Surgery for Pancreatic Cancer.Journal of gastrointestinal cancer · 2025Observational
- Caspase-independent cell death in lung cancer: from mechanisms to clinical applications.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Article
- CES1 is associated with cisplatin resistance and poor prognosis of head and neck squamous cell carcinoma.Oncology research · 2024Article
- Tobacco nicotine promotes TRAIL resistance in lung cancer through SNHG5.Experimental and therapeutic medicine · 2023Article
- The Association between Smoking and Mortality in Women with Breast Cancer: A Real-World Database Analysis.Cancers · 2022Article
- β-Caryophyllene Counteracts Chemoresistance Induced by Cigarette Smoke in Triple-Negative Breast Cancer MDA-MB-468 Cells.Biomedicines · 2022Article
- Nicotine-induced miR-21-3p promotes chemoresistance in lung cancer by negatively regulating FOXO3a.Oncology letters · 2022Article
- Study protocol for a hybrid type 1 effectiveness-implementation trial testing virtual tobacco treatment in oncology practices [Smokefree Support Study 2.0].BMC public health · 2022Article
- Review
- Nicotinic receptors modulate antitumor therapy response in triple negative breast cancer cells.World journal of clinical oncology · 2022Article
- Nicotine Changes Airway Epithelial Phenotype and May Increase the SARS-COV-2 Infection Severity.Molecules (Basel, Switzerland) · 2020Article
- Can Cancer Diagnosis Help in Quitting Tobacco? Barriers and Enablers to Tobacco Cessation Among Head and Neck Cancer Patients from a Tertiary Cancer Center in South india.Indian journal of psychological medicine · 2020Article
- Impact of the APE1 Redox Function Inhibitor E3330 in Non-small Cell Lung Cancer Cells Exposed to Cisplatin: Increased Cytotoxicity and Impairment of Cell Migration and Invasion.Antioxidants (Basel, Switzerland) · 2020Article
- Nicotine exposure potentiates lung tumorigenesis by perturbing cellular surveillance.British journal of cancer · 2020Article
- SNHG9 was upregulated in NSCLC and associated with DDP-resistance and poor prognosis of NSCLC patients.American journal of translational research · 2020Article
- Nicotinic-nAChR signaling mediates drug resistance in lung cancer.Journal of Cancer · 2020Review
- Mitochondria as a possible target for nicotine action.Journal of bioenergetics and biomembranes · 2019Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Continued smoking causes tumor progression and resistance to therapy in lung cancer. Carcinogens possess the ability to block apoptosis, and thus may induce development of cancers and resistance to therapy. Tobacco carcinogens have been studied widely; however, little is known about the agents that inhibit apoptosis, such as nicotine. We determine whether mitochondrial signaling mediates antiapoptotic effects of nicotine in lung cancer. A549 cells were exposed to nicotine (1 muM) followed by cisplatin (35 muM) plus etoposide (20 muM) for 24 hours. We found that nicotine prevented chemotherapy-induced apoptosis, improved cell survival, and caused modest increases in DNA synthesis. Inhibition of mitogen-activated protein kinase (MAPK) and Akt prevented the antiapoptotic effects of nicotine and decreased chemotherapy-induced apoptosis. Small interfering RNA MAPK kinase-1 blocked antiapoptotic effects of nicotine, whereas small interfering RNA MAPK kinase-2 blocked chemotherapy-induced apoptosis. Nicotine prevented chemotherapy-induced reduction in mitochondrial membrane potential and caspase-9 activation. Antiapoptotic effects of nicotine were blocked by mitochondrial anion channel inhibitor, 4,4'diisothiocyanatostilbene-2,2'disulfonic acid. Chemotherapy enhanced translocation of proapoptotic Bax to the mitochondria, whereas nicotine blocked these effects. Nicotine up-regulated Akt-mediated antiapoptotic X-linked inhibitor of apoptosis protein and phosphorylated proapoptotic Bcl2-antagonist of cell death. The A549-rho0 cells, which lack mitochondrial DNA, demonstrated partial resistance to chemotherapy-induced apoptosis, but blocked the antiapoptotic effects of nicotine. Accordingly, we provide evidence that nicotine modulates mitochondrial signaling and inhibits chemotherapy-induced apoptosis in lung cancer. The mitochondrial regulation of nicotine imposes an important mechanism that can critically impair the treatment of lung cancer, because many cancer-therapeutic agents induce apoptosis via the mitochondrial death pathway. Strategies aimed at understanding nicotine-mediated signaling may facilitate the development of improved therapies in lung cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.