ArticleExperimental & molecular medicine2020
A novel PPARɣ ligand, PPZ023, overcomes radioresistance via ER stress and cell death in human non-small-cell lung cancer cells.
Article in Experimental & molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 22 citations in OpenAlex.
- Endoplasmic reticulum stress-mediated programmed cell death in the tumor microenvironment.Cell death discovery · 2025Review
- Impacts of co-mutations in oligometastatic and oligoprogressive non-small cell lung cancer withTranslational lung cancer research · 2025Review
- Endoplasmic reticulum stress in non-small cell lung cancer: a review of therapeutic agents, mechanistic insights, and implications for therapy.Frontiers in cell and developmental biology · 2025Review
- Discovery of a novel binding pocket in PPARγ for partial agonists: structure-based virtual screening identifies ginsenoside Rg5 as a partial agonist promoting beige adipogenesis.Frontiers in chemistry · 2025Article
- PPARγ Modulators in Lung Cancer: Molecular Mechanisms, Clinical Prospects, and Challenges.Biomolecules · 2024Review
- Effect of eIF2α in Neuronal Injury Induced by High Glucose and the Protective Mechanism of Resveratrol.Molecular neurobiology · 2023Article
- ADAR1 is a prognostic biomarker and is correlated with immune infiltration in lung adenocarcinoma.Cancer medicine · 2023Article
- Unfolded protein response and angiogenesis in malignancies.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- Targeting Mitochondrial Metabolism to Reverse Radioresistance: An Alternative to Glucose Metabolism.Antioxidants (Basel, Switzerland) · 2022Review
- Current Landscape of Therapeutic Resistance in Lung Cancer and Promising Strategies to Overcome Resistance.Cancers · 2022Review
- Targeting Nuclear Receptors in Lung Cancer-Novel Therapeutic Prospects.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Interactions between endoplasmic reticulum stress and extracellular vesicles in multiple diseases.Frontiers in immunology · 2022Review
- Circular RNA circβ-catenin aggravates the malignant phenotype of non-small-cell lung cancer via encoding a peptide.Journal of clinical laboratory analysis · 2021Article
- The Novel Benzothiazole Derivative PB11 Induces Apoptosis via the PI3K/AKT Signaling Pathway in Human Cancer Cell Lines.International journal of molecular sciences · 2021Article
- Article
- Traditional Chinese Medicine Xihuang Wan Inhibited Lewis Lung Carcinoma in a Syngeneic Model, Equivalent to Cytotoxic Chemotherapy, by Altering Multiple Signaling Pathways.In vivo (Athens, Greece)Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Peroxisome proliferator-activated receptor gamma (PPARɣ) agonists exert powerful anticancer effects by suppressing tumor growth. In this study, we developed PPZ023 (1-(2-(ethylthio)benzyl)-4-(2-methoxyphenyl)piperazine), a novel PPAR ligand candidate, and investigated the underlying signaling pathways in both non-small-cell lung cancer (NSCLC) and radio-resistant NSCLC cells. To identify whether PPZ023 has anticancer effects in NSCLC and radioresistant NSCLC cells, we performed WST-1, LDH, Western blot, and caspase-3 and -9 activity assays. Furthermore, we isolated exosomes from PPZ023-treated NSCLC cells and studied cell death signaling. PPZ023 reduces cell viability and increases LDH cytotoxicity and caspase-3 activity in NSCLC cells. PPZ023 induces cell death by generating reactive oxygen species (ROS) and triggering mitochondrial cytochrome c release. PPZ023 treatment causes cell death via the PERK-eIF2α-CHOP axis in both NSCLC cell lysates and exosomes, and PERK and CHOP knockdown significantly blocks ER stress-mediated apoptosis by reducing cleaved caspase-3. Interestingly, diphenyleneiodonium (DPI, a Nox inhibitor) inhibits PPZ023-induced cell death via ER stress, and PPARɣ knockdown inhibits PPZ023-induced ROS, ER stress, and cell death. Moreover, PPZ023, in combination with radiation, causes synergic cell death via exosomal ER stress in radioresistant NSCLC cells, indicating that PPZ023/radiation overcomes radioresistance. Taken together, our results suggest that PPZ023 is a powerful anticancer reagent for overcoming radioresistance.
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.