ArticlePloS one2013
Shikonin kills glioma cells through necroptosis mediated by RIP-1.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 135 citations in OpenAlex.
- Ascorbate-driven quinone redox cycling as a pro-oxidant anticancer strategy.Redox biology · 2026Review
- Expression of Concern: Shikonin Kills Glioma Cells through Necroptosis Mediated by RIP-1.PloS one · 2026Article
- Shikonin inhibits epithelial-mesenchymal transition in glioblastoma cells by upregulating p53 and promoting miR-361-5p level to suppress ZEB1 expression.BMC neuroscience · 2025Article
- Preparation of surface-modified PLGA nanoparticles containing carbon quantum dots: insights from C6 cell line assays.Nanomedicine (London, England) · 2025Article
- Nanosized Shikonin Disrupts Tumor-Cell Mismatch Repair and Synergizes with Manganese to Sensitize Squamous Carcinoma to Immunotherapy.ACS nano · 2025Article
- A novel approach to glioblastoma multiforme treatment using modulation of key pathways by naturally occurring small molecules.Inflammopharmacology · 2025Review
- The Small Molecules of Plant Origin with Anti-Glioma Activity.International journal of molecular sciences · 2025Review
- In Vitro Antitumor and Antimetastatic Activity of a New Lapachol Derivative against Metastatic Breast Carcinoma.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Analysis of Antiangiogenic Potential and Cell Death Mechanism of a Kinetically Inert Platinum Antitumor Agent.ACS medicinal chemistry letters · 2024Article
- Combination chemotherapy via poloxamer 188 surface-modified PLGA nanoparticles that traverse the blood-brain-barrier in a glioblastoma model.Scientific reports · 2024Article
- Tumor biomarkers for diagnosis, prognosis and targeted therapy.Signal transduction and targeted therapy · 2024Review
- Shikonin Induces Glioma Necroptosis, Stemness Decline, and Impedes (Immuno)Proteasome Activity.Stem cells international · 2024Article
- Comparative mechanistic study of RPE cell death induced by different oxidative stresses.Redox biology · 2023Article
- The amide derivative of anticopalic acid induces non-apoptotic cell death in triple-negative breast cancer cells by inhibiting FAK activation.Scientific reports · 2023Article
- A bibliometric analysis of ferroptosis, necroptosis, pyroptosis, and cuproptosis in cancer from 2012 to 2022.Cell death discovery · 2023Article
- Harnessing Folate-Functionalized Nasal Delivery of Dox-Erlo-Loaded Biopolymeric Nanoparticles in Cancer Treatment: Development, Optimization, Characterization, and Biodistribution Analysis.Pharmaceuticals (Basel, Switzerland) · 2023Article
- TRAF6 regulates the abundance of RIPK1 and inhibits the RIPK1/RIPK3/MLKL necroptosis signaling pathway and affects the progression of colorectal cancer.Cell death & disease · 2023Article
- Induction of RIPK3/MLKL-mediated necroptosis by Erigeron breviscapus injection exhibits potent antitumor effect.Frontiers in pharmacology · 2023Article
- Sonosensitizer Nanoplatforms Augmented Sonodynamic Therapy-Sensitizing Shikonin-Induced Necroptosis Against Hepatocellular Carcinoma.International journal of nanomedicine · 2023Article
- Potent Ruthenium-Ferrocene Bimetallic Antitumor Antiangiogenic Agent That Circumvents Platinum Resistance: From Synthesis and Mechanistic Studies toJournal of medicinal chemistry · 2022Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
- Expression of concern
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeShikonin was reported to induce necroptosis in leukemia cells, but apoptosis in glioma cell lines. Thus, it is needed to clarify whether shikonin could cause necroptosis in glioma cells and investigate its underlying mechanisms.
methodsShikonin and rat C6 glioma cell line and Human U87 glioma cell line were used in this study. The cellular viability was assayed by MTT. Flow cytometry with annexin V-FITC and PI double staining was used to analyze cellular death modes. Morphological alterations in C6 glioma cells treated with shikoinin were evaluated by electronic transmission microscopy and fluorescence microscopy with Hoechst 33342 and PI double staining. The level of reactive oxygen species was assessed by using redox-sensitive dye DCFH-DA. The expressional level of necroptosis associated protein RIP-1 was analyzed by western blotting.
resultsShikonin induced cell death in C6 and U87 glioma cells in a dose and time dependent manner. The cell death in C6 and U87 glioma cells could be inhibited by necroptosis inhibitor necrotatin-1, not by pan-caspase inhibitor z-VAD-fmk. Shikonin treated C6 glioma cells presented electron-lucent cytoplasm, loss of plasma membrane integrity and intact nuclear membrane in morphology. The increased ROS level caused by shikonin was attenuated by necrostatin-1 and blocking ROS by anti-oxidant NAC rescued shikonin-induced cell death in both C6 and U87 glioma cells. Moreover, the expressional level of RIP-1 was up-regulated by shikonin in a dose and time dependent manner as well, but NAC suppressed RIP-1 expression.
conclusionsWe demonstrated that the cell death caused by shikonin in C6 and U87 glioma cells was mainly via necroptosis. Moreover, not only RIP-1 pathway, but also oxidative stress participated in the activation of shikonin induced necroptosis.
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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.