ArticleCell death & disease2014
Mitochondrial inhibitor sensitizes non-small-cell lung carcinoma cells to TRAIL-induced apoptosis by reactive oxygen species and Bcl-X(L)/p53-mediated amplification mechanisms.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- A Darwinian Perspective on Tumor Evolution.International journal of biological sciences · 2026Review
- Neuroprotective Effect of Cannabidiol Against Rotenone in Hippocampal Neuron Culture.Chemistry, an Asian journal · 2025Article
- Article
- Lung adenocarcinoma-related target gene prediction and drug repositioning.Frontiers in pharmacology · 2022Article
- HERB: a high-throughput experiment- and reference-guided database of traditional Chinese medicine.Nucleic acids research · 2021Article
- A Combined Phytochemistry and Network Pharmacology Approach to Reveal Potential Anti-NSCLC Effective Substances and Mechanisms inFrontiers in pharmacology · 2021Article
- Rotenone exerts developmental neurotoxicity in a human brain spheroid model.Toxicology and applied pharmacology · 2018Article
- A small compound spindlactone A sensitizes human endometrial cancer cells to TRAIL-induced apoptosis via the inhibition of NAD(P)H dehydrogenase quinone 1.OncoTargets and therapy · 2018Article
- Bufalin sensitizes human bladder carcinoma cells to TRAIL-mediated apoptosis.Oncology letters · 2017Article
- Mechanistic Investigations of the Mitochondrial Complex I Inhibitor Rotenone in the Context of Pharmacological and Safety Evaluation.Scientific reports · 2017Article
- Reversal of the Apoptotic Resistance of Non-Small-Cell Lung Carcinoma towards TRAIL by Natural Product Toosendanin.Scientific reports · 2017Article
- Myosin IIA-related Actomyosin Contractility Mediates Oxidative Stress-induced Neuronal Apoptosis.Frontiers in molecular neuroscience · 2017Article
- Migration and invasion of drug-resistant lung adenocarcinoma cells are dependent on mitochondrial activity.Experimental & molecular medicine · 2016Article
- ROS homeostasis and metabolism: a dangerous liason in cancer cells.Cell death & disease · 2016Review
- Ethanolic extract of Descurainia sophia seeds sensitizes A549 human lung cancer cells to TRAIL cytotoxicity by upregulating death receptors.BMC complementary and alternative medicine · 2016Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising agent for anticancer therapy; however, non-small-cell lung carcinoma (NSCLC) cells are relatively TRAIL resistant. Identification of small molecules that can restore NSCLC susceptibility to TRAIL-induced apoptosis is meaningful. We found here that rotenone, as a mitochondrial respiration inhibitor, preferentially increased NSCLC cells sensitivity to TRAIL-mediated apoptosis at subtoxic concentrations, the mechanisms by which were accounted by the upregulation of death receptors and the downregulation of c-FLIP (cellular FLICE-like inhibitory protein). Further analysis revealed that death receptors expression by rotenone was regulated by p53, whereas c-FLIP downregulation was blocked by Bcl-X(L) overexpression. Rotenone triggered the mitochondria-derived reactive oxygen species (ROS) generation, which subsequently led to Bcl-X(L) downregulation and PUMA upregulation. As PUMA expression was regulated by p53, the PUMA, Bcl-X(L) and p53 in rotenone-treated cells form a positive feedback amplification loop to increase the apoptosis sensitivity. Mitochondria-derived ROS, however, promote the formation of this amplification loop. Collectively, we concluded that ROS generation, Bcl-X(L) and p53-mediated amplification mechanisms had an important role in the sensitization of NSCLC cells to TRAIL-mediated apoptosis by rotenone. The combined TRAIL and rotenone treatment may be appreciated as a useful approach for the therapy of NSCLC that warrants further investigation.
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