ArticleScientific reports2016
Miltirone exhibits antileukemic activity by ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction pathways.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 55 citations in OpenAlex.
- Piperine Induces Apoptosis and Cell Cycle Arrest via Multiple Oxidative Stress Mechanisms and Regulation of PI3K/Akt and MAPK Signaling in Colorectal Cancer Cells.Antioxidants (Basel, Switzerland) · 2025Article
- PERK-Olating Through Cancer: A Brew of Cellular Decisions.Biomolecules · 2025Review
- Miltirone enhances the chemosensitivity of gastric cancer cells to cisplatin by suppressing the PI3K/AKT signaling pathway.Frontiers in pharmacology · 2025Article
- Selenomethionine Attenuated HAntioxidants (Basel, Switzerland) · 2023Article
- Manoalide Induces Intrinsic Apoptosis by Oxidative Stress and Mitochondrial Dysfunction in Human Osteosarcoma Cells.Antioxidants (Basel, Switzerland) · 2023Article
- In Silico and In Vitro Identification of P-Glycoprotein Inhibitors from a Library of 375 Phytochemicals.International journal of molecular sciences · 2023Article
- Diplacone Isolated fromInternational journal of molecular sciences · 2023Article
- Pyroptosis: shedding light on the mechanisms and links with cancers.Frontiers in immunology · 2023Review
- Pyroptosis and pyroptosis-inducing cancer drugs.Acta pharmacologica Sinica · 2022Review
- Prostate Apoptosis Response-4 (Par-4): A Novel Target in Pyronaridine-Induced Apoptosis in Glioblastoma (GBM) Cells.Cancers · 2022Article
- Hexokinase 3 enhances myeloid cell survival via non-glycolytic functions.Cell death & disease · 2022Article
- ER Stress and Unfolded Protein Response in Leukemia: Friend, Foe, or Both?Biomolecules · 2021Review
- Miltirone induces cell death in hepatocellular carcinoma cell through GSDME-dependent pyroptosis.Acta pharmaceutica Sinica. B · 2020Article
- Tannic acid inhibits lipid metabolism and induce ROS in prostate cancer cells.Scientific reports · 2020Article
- The Role of Reactive Oxygen Species in Acute Myeloid Leukaemia.International journal of molecular sciences · 2019Review
- Calreticulin Ins5 and Del52 mutations impair unfolded protein and oxidative stress responses in K562 cells expressing CALR mutants.Scientific reports · 2019Article
- Pharmacological actions of miltirone in the modulation of platelet function.Acta pharmacologica Sinica · 2019Article
- Miltirone-induced apoptosis in cisplatin-resistant lung cancer cells through upregulation of p53 signaling pathways.Oncology letters · 2018Article
- Apoptotic and Anti-Inflammatory Effects ofBioMed research international · 2018Article
- The novel resveratrol derivative 3,5-diethoxy-3',4'-dihydroxy-trans-stilbene induces mitochondrial ROS-mediated ER stress and cell death in human hepatoma cells in vitro.Acta pharmacologica Sinica · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this study, we investigated the effects of miltirone in human leukemia cell lines, primary leukemia cells, and nude mice U937 xenograft. Treatment of cells with miltirone resulted in apoptosis, mitochondria membrane potential (MMP) collapses, increase of Bax/Bcl-2 ratio, and cytochrome c release. Miltirone triggered the endoplasmic reticulum (ER) stress identified through several key molecules of the unfolded protein response, including phosphorylated PERK, eIF2a, GRP78, GRP94, and caspase-12. Miltrone treatment also resulted in the release of Ca(2+) from the ER stores and mitochondrial Ca(2+) loading in the cells. Further research revealed that miltirone resulted in dose-dependent decrease in complex III activity and elevated reactive oxygen species (ROS) production in these cells. Miltirone-induced apoptosis, dissipation of MMP and ER stress were dramatically blocked by pretreatment with antioxidant N-acetylcysteine (NAC). In contrast, treatment with ER stress inhibitor TUDCA significantly attenuated miltirone-induced ROS and apoptosis in leukemia cells. Moreover, our in vivo findings showed that administration of miltirone markedly inhibited tumor growth and induced apoptosis in U937 xenograft model with low systemic toxicity. Taken together, these findings indicate that miltirone may exert its antileukemic activity by inducing apoptosis through a ROS-dependent destructive cycle involving ER stress and mitochondrial dysfunction.
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