ArticlePloS one2015
The Roles of ROS and Caspases in TRAIL-Induced Apoptosis and Necroptosis in Human Pancreatic Cancer Cells.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 84 citations in OpenAlex.
- βIII-tubulin can act as a brake on extrinsic apoptosis in pancreatic cancer.Cell death & disease · 2026Article
- Article
- Inhibition of UBE2N enhances TRAIL-mediated apoptosis through upregulation of DR5 in cancer cells.International journal of medical sciences · 2026Article
- Low extracellular pH enhances TRAIL-induced apoptosis by downregulating Mcl-1 expression.Experimental cell research · 2025Article
- Improvement of Therapeutic Effect via Inducing Non-Apoptotic Cell Death Using mRNA-Protection Nanocage.Advanced healthcare materials · 2024Article
- ARHGAP15 promotes metastatic colonization in gastric cancer by suppressing RAC1-ROS pathway.PLoS genetics · 2023Article
- Cyanidin-3-O-Glucoside Induces the Apoptosis of Human Gastric Cancer MKN-45 Cells through ROS-Mediated Signaling Pathways.Molecules (Basel, Switzerland) · 2023Article
- Bufalin Induces Programmed Necroptosis in Triple-Negative Breast Cancer Drug-Resistant Cell Lines through RIP1/ROS-Mediated Pathway.Chinese journal of integrative medicine · 2022Article
- Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy.Signal transduction and targeted therapy · 2022Review
- Understanding Necroptosis in Pancreatic Diseases.Biomolecules · 2022Review
- Synthesis and Antiproliferative Activity of Novel Imipridone-Ferrocene Hybrids with Triazole and Alkyne Linkers.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Astaxanthin Sensitizes Low SOD2-Expressing GBM Cell Lines to TRAIL Treatment via Pathway Involving Mitochondrial Membrane Depolarization.Antioxidants (Basel, Switzerland) · 2022Article
- Targeting Drug Chemo-Resistance in Cancer Using Natural Products.Biomedicines · 2021Review
- The molecular mechanism of acute liver injury and inflammatory response induced by Concanavalin A.Molecular biomedicine · 2021Article
- Detection of Oxidative Stress Induced by Nanomaterials in Cells-The Roles of Reactive Oxygen Species and Glutathione.Molecules (Basel, Switzerland) · 2021Review
- Calotropis gigantea stem bark extract induced apoptosis related to ROS and ATP production in colon cancer cells.PloS one · 2021Article
- Reactive Oxygen Species (ROS) Regulates Different Types of Cell Death by Acting as a Rheostat.Oxidative medicine and cellular longevity · 2021Review
- Sulphamoylated Estradiol Analogue Induces Reactive Oxygen Species Generation to Exert Its Antiproliferative Activity in Breast Cancer Cell Lines.Molecules (Basel, Switzerland) · 2020Article
- Mechanism and significance of apoptosis of the immortalized human oral mucosal epithelial cells established by Lentivirus-mediated hTERT.Molecular biology reports · 2020Article
- The NovelInternational journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Death signaling provided by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) can induce death in cancer cells with little cytotoxicity to normal cells; this cell death has been thought to involve caspase-dependent apoptosis. Reactive oxygen species (ROS) are also mediators that induce cell death, but their roles in TRAIL-induced apoptosis have not been elucidated fully. In the current study, we investigated ROS and caspases in human pancreatic cancer cells undergoing two different types of TRAIL-induced cell death, apoptosis and necroptosis. TRAIL treatment increased ROS in two TRAIL-sensitive pancreatic cancer cell lines, MiaPaCa-2 and BxPC-3, but ROS were involved in TRAIL-induced apoptosis only in MiaPaCa-2 cells. Unexpectedly, inhibition of ROS by either N-acetyl-L-cysteine (NAC), a peroxide inhibitor, or Tempol, a superoxide inhibitor, increased the annexin V-/propidium iodide (PI)+ early necrotic population in TRAIL-treated cells. Additionally, both necrostatin-1, an inhibitor of receptor-interacting protein kinase 1 (RIP1), and siRNA-mediated knockdown of RIP3 decreased the annexin V-/PI+ early necrotic population after TRAIL treatment. Furthermore, an increase in early apoptosis was induced in TRAIL-treated cancer cells under inhibition of either caspase-2 or -9. Caspase-2 worked upstream of caspase-9, and no crosstalk was observed between ROS and caspase-2/-9 in TRAIL-treated cells. Together, these results indicate that ROS contribute to TRAIL-induced apoptosis in MiaPaCa-2 cells, and that ROS play an inhibitory role in TRAIL-induced necroptosis of MiaPaCa-2 and BxPC-3 cells, with caspase-2 and -9 playing regulatory roles in this process.
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