ArticleApoptosis : an international journal on programmed cell death2019
JNK inhibition blocks piperlongumine-induced cell death and transcriptional activation of heme oxygenase-1 in pancreatic cancer cells.
Article in Apoptosis : an international journal on programmed cell death, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 46 citations in OpenAlex.
- Plant-Derived Natural Products and Selective Apoptosis: A Cancer-Cell Vulnerability-State Framework from Redox Imbalance to Membrane-Ion Dysregulation.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Piplartine as an Innovative Natural Product With Dual Antiparasitic and Immunomodulatory Actions.Journal of immunology research · 2026Review
- Piperlongumine induces meningioma cell death via the ROS-mediated endoplasmic reticulum stress and the alteration of the ubiquitin-proteasome system.Journal of neuro-oncology · 2025Article
- Mechanism of miR-107/HMOX1 axis in hepatic sinusoidal endothelial cells stimulated by ischemia-reperfusion injury.Hereditas · 2025Article
- GSTP1 knockdown induces metabolic changes affecting energy production and lipid balance in pancreatic cancer cells.Molecular & cellular oncology · 2025Article
- The molecular mechanism of PLD2-mediated regulation of apoptosis and cell edema in pancreatic cells via the Nrf2/NF-κB pathway.Scientific reports · 2024Article
- The protective effect of imatinib against pancreatic β-cell apoptosis induced by dexamethasone via increased GSTP1 expression and reduced oxidative stress.Scientific reports · 2024Article
- Ferroptosis-Regulated Natural Products and miRNAs and Their Potential Targeting to Ferroptosis and Exosome Biogenesis.International journal of molecular sciences · 2024Review
- The Antitumor Activity of Piplartine: A Review.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Piperlongumine Induces Cellular Apoptosis and Autophagy via the ROS/Akt Signaling Pathway in Human Follicular Thyroid Cancer Cells.International journal of molecular sciences · 2023Article
- 3,4‑Dihydroxyacetophenone attenuates oxidative stress‑induced damage to HUVECs via regulation of the Nrf2/HO‑1 pathway.Molecular medicine reports · 2022Article
- Can Scoliotic Discs Be Controls for Molecular Studies in Intervertebral Disc Research? Insights From Proteomics.Global spine journal · 2022Article
- Systems biology reveals anatabine to be an NRF2 activator.Frontiers in pharmacology · 2022Article
- Expression Dynamics of Heme Oxygenase-1 in Tumor Cells and the Host Contributes to the Progression of Tumors.Journal of personalized medicine · 2021Article
- Article
- Biomarkers and Mechanisms of Oxidative Stress-Last 20 Years of Research with an Emphasis on Kidney Damage and Renal Transplantation.International journal of molecular sciences · 2021Review
- GSTP1 as a novel target in radiation induced lung injury.Journal of translational medicine · 2021Review
- Piperlongumine promotes death of retinoblastoma cancer cells.Oncotarget · 2021Article
- Stress-driven cardiac calcium mishandling via a kinase-to-kinase crosstalk.Pflugers Archiv : European journal of physiology · 2021Review
- Heme oxygenase 1: a novel oncogene in multiple gynecological cancers.International journal of biological sciences · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Piperlongumine (PL) is an alkaloid that inhibits glutathione S-transferase pi 1 (GSTP1) activity, resulting in elevated reactive oxygen species (ROS) levels and cancer-selective cell death. We aimed to identify stress-associated molecular responses to PL treatment in pancreatic ductal adenocarcinoma (PDAC) cells. GSTP1 directly interacts with JNK, which is activated by oxidative stress and can lead to decreased cancer cell proliferation and cell death. Therefore, we hypothesized that JNK pathways are activated in response to PL treatment. Our results show PL causes dissociation of GSTP1 from JNK; robust JNK, c-Jun, and early ERK activation followed by suppression; increased expression of cleaved caspase-3 and cleaved PARP; and nuclear translocation of Nrf2 and c-Myc in PDAC cells. Gene expression analysis revealed PL caused a > 20-fold induction of heme oxygenase-1 (HO-1), which we hypothesized was a survival mechanism for PDAC cells under enhanced oxidative stress. HO-1 knockout resulted in enhanced PL-induced PDAC cell death under hypoxic conditions. Similarly, high concentrations of the HO-1 inhibitor, ZnPP (10 µM), sensitized PDAC cells to PL; however, lower concentrations ZnPP (10 nM) and high or low concentrations of SnPP both protected PDAC cells from PL-induced cell death. Interestingly, the JNK inhibitor significantly blocked PL-induced PDAC cell death, Nrf-2 nuclear translocation, and HMOX-1 mRNA expression. Collectively, the results demonstrate JNK signaling contributes to PL-induced PDAC cell death, and at the same time, activates Nrf-2 transcription of HMOX-1 as a compensatory survival mechanism. These results suggest that elevating oxidative stress (using PL) while at the same time impairing antioxidant capacity (inhibiting HO-1) may be an effective therapeutic approach for PDAC.
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Registered trials
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