ArticleCell death & disease2011
Chemosensitization by phenothiazines in human lung cancer cells: impaired resolution of γH2AX and increased oxidative stress elicit apoptosis associated with lysosomal expansion and intense vacuolation.
Article in Cell death & disease, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 60 citations in OpenAlex.
- Multi-Target Antitumor Effects of Natural Products and Approved Drug Repurposing in Non-Small Cell Lung Cancer: Advances in Mechanisms, Combination Regimens, Delivery System Optimization, and Clinical Challenges.International journal of molecular sciences · 2026Review
- Drug repositioning: examining antipsychotic drugs and their anticancer effects.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2025Review
- Targeting Lysosomes: A Strategy Against Chemoresistance in Cancer.Mini reviews in medicinal chemistry · 2024Review
- Article
- KLF14 regulates the growth of hepatocellular carcinoma cells via its modulation of iron homeostasis through the repression of iron-responsive element-binding protein 2.Journal of experimental & clinical cancer research : CR · 2023Article
- Antipsychotic Drug Fluphenazine against Human Cancer Cells.Biomolecules · 2022Review
- Anti-glioblastoma activity of monensin and its analogs in an organoid model of cancer.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Article
- Synergic effect of anticancer peptide CIGB-552 and Cisplatin in lung cancer models.Molecular biology reports · 2022Article
- ERα-related chromothripsis enhances concordant gene transcription on chromosome 17q11.1-q24.1 in luminal breast cancer.BMC medical genomics · 2020Article
- The Combined Use of Phenothiazines and Statins Strongly Affects Doxorubicin-Resistance, Apoptosis, and Cox-2 Activity in Colon Cancer Cells.International journal of molecular sciences · 2019Article
- Discovery of Small Molecules That Induce Lysosomal Cell Death in Cancer Cell Lines Using an Image-Based Screening Platform.Assay and drug development technologies · 2016Article
- Pharmacological exploitation of the phenothiazine antipsychotics to develop novel antitumor agents-A drug repurposing strategy.Scientific reports · 2016Article
- Aberrant Apoptotic Response of Colorectal Cancer Cells to Novel Nucleoside Analogues.PloS one · 2015Article
- Toxic effects of xylazine on endothelial cells in combination with cocaine and 6-monoacetylmorphine.Toxicology in vitro : an international journal published in association with BIBRA · 2014Article
- Harnessing the lysosome-dependent antitumor activity of phenothiazines in human small cell lung cancer.Cell death & disease · 2014Article
- Phenothiazine Inhibitors of TLKs Affect Double-Strand Break Repair and DNA Damage Response Recovery and Potentiate Tumor Killing with Radiomimetic Therapy.Genes & cancer · 2013Article
- NRF2 and p53: Januses in cancer?Oncotarget · 2012Review
- Analysis of apoptosis methods recently used in Cancer Research and Cell Death & Disease publications.Cell death & disease · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemotherapy resistance poses severe limitations on the efficacy of anti-cancer medications. Recently, the notion of using novel combinations of 'old' drugs for new indications has garnered significant interest. The potential of using phenothiazines as chemosensitizers has been suggested earlier but so far our understanding of their molecular targets remains scant. The current study was designed to better define phenothiazine-sensitive cellular processes in relation to chemosensitivity. We found that phenothiazines shared the ability to delay γH2AX resolution in DNA-damaged human lung cancer cells. Accordingly, cells co-treated with chemotherapy and phenothiazines underwent protracted cell-cycle arrest followed by checkpoint escape that led to abnormal mitoses, secondary arrest and/or a form of apoptosis associated with increased endogenous oxidative stress and intense vacuolation. We provide evidence implicating lysosomal dysfunction as a key component of cell death in phenothiazine co-treated cells, which also exhibited more typical hallmarks of apoptosis including the activation of both caspase-dependent and -independent pathways. Finally, we demonstrated that vacuolation in phenothiazine co-treated cells could be reduced by ROS scavengers or the vacuolar ATPase inhibitor bafilomycin, leading to increased cell viability. Our data highlight the potential benefit of using phenothiazines as chemosensitizers in tumors that acquire molecular alterations rendering them insensitive to caspase-mediated apoptosis.
Indexed as
Identifiers
What OpenQuestion holds
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.