ArticleNeuro-oncology2014
Piperlongumine treatment inactivates peroxiredoxin 4, exacerbates endoplasmic reticulum stress, and preferentially kills high-grade glioma cells.
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Article in Neuro-oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32citing papers in PubMed
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Who cites it
32 citing papers in PubMed, 66 citations in OpenAlex.
- Article
- Carbonic Anhydrase Inhibition Sensitizes Group 3 Medulloblastoma to Radiotherapy.Cancer research · 2025Article
- Piperlongumine Inhibits Lung Cancer Growth by Inducing Endoplasmic Reticulum Stress Leading to Suppression of M2 Macrophage Polarization.Biological procedures online · 2025Article
- Peroxiredoxin 6 maintains mitochondrial homeostasis and promotes tumor progression through ROS/JNK/p38 MAPK signaling pathway in multiple myeloma.Scientific reports · 2025Article
- Endoplasmic Reticulum Stress in Gliomas: Exploiting a Dual-Effect Dysfunction through Chemical Pharmaceutical Compounds and Natural Derivatives for Therapeutical Uses.International journal of molecular sciences · 2024Review
- Combination therapy with HSP90 inhibitors and piperlongumine promotes ROS-mediated ER stress in colon cancer cells.Cell death discovery · 2023Article
- The Antitumor Activity of Piplartine: A Review.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Identification of Piperlongumine as Potent Inhibitor of Necroptosis.Drug design, development and therapy · 2023Article
- Essential Roles of Peroxiredoxin IV in Inflammation and Cancer.Molecules (Basel, Switzerland) · 2022Review
- Piperlongumine combined with vitamin C as a new adjuvant therapy against gastric cancer regulates the ROS-STAT3 pathway.The Journal of international medical research · 2022Article
- Cysteine cathepsin C: a novel potential biomarker for the diagnosis and prognosis of glioma.Cancer cell international · 2022Article
- Characterization of an endoplasmic reticulum stress-related signature to evaluate immune features and predict prognosis in glioma.Journal of cellular and molecular medicine · 2021Article
- The promising potential of piperlongumine as an emerging therapeutics for cancer.Exploration of targeted anti-tumor therapy · 2021Review
- The Synergistic Effect of Piperlongumine and Sanguinarine on the Non-Small Lung Cancer.Molecules (Basel, Switzerland) · 2020Article
- Piperlongumine Attenuates High Calcium/Phosphate-Induced Arterial Calcification by Preserving P53/PTEN Signaling.Frontiers in cardiovascular medicine · 2020Article
- Piperlongumine Acts as an Immunosuppressant by Exerting Prooxidative Effects in Human T Cells Resulting in Diminished TFrontiers in immunology · 2020Article
- Targeting NRF2, Regulator of Antioxidant System, to Sensitize Glioblastoma Neurosphere Cells to Radiation-Induced Oxidative Stress.Oxidative medicine and cellular longevity · 2020Article
- Piperlongumine potentiates the antitumor efficacy of oxaliplatin through ROS induction in gastric cancer cells.Cellular oncology (Dordrecht, Netherlands) · 2019Article
- NFBTA: A Potent Cytotoxic Agent against Glioblastoma.Molecules (Basel, Switzerland) · 2019Article
- Radioprotective Role of Peroxiredoxin 6.Antioxidants (Basel, Switzerland) · 2019Review
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Authors and funding
11 authors at 4 institutions in 1 country.
Tae Hyong KimDardinger Neuro-oncology Center, Department of Neurological Surgery, Ohio State University, Columbus, Ohio (T.H.K., J.S., S.-H.K., A.K.P., I.N., B.K., C.-H.K.); Solid Tumor Program at the James Comprehensive Cancer Center, Columbus, Ohio (T.H.K., J.S., A.K.P., C.-H.K.); Center for Biostatistics, Ohio State University, Columbus, Ohio (X.M.); Department of Radiation Oncology, Ohio State University, Columbus, Ohio (K.P.); Division of Hematology, Department of Internal Medicine, Ohio State University, Columbus, Ohio (J.Y.); Department of Molecular and Cellular Biochemistry, Ohio State University Wexner Medical Center, Columbus, Ohio (S.O.Y.).
Jieun SongDardinger Neuro-oncology Center, Department of Neurological Surgery, Ohio State University, Columbus, Ohio (T.H.K., J.S., S.-H.K., A.K.P., I.N., B.K., C.-H.K.); Solid Tumor Program at the James Comprehensive Cancer Center, Columbus, Ohio (T.H.K., J.S., A.K.P., C.-H.K.); Center for Biostatistics, Ohio State University, Columbus, Ohio (X.M.); Department of Radiation Oncology, Ohio State University, Columbus, Ohio (K.P.); Division of Hematology, Department of Internal Medicine, Ohio State University, Columbus, Ohio (J.Y.); Department of Molecular and Cellular Biochemistry, Ohio State University Wexner Medical Center, Columbus, Ohio (S.O.Y.).
Sung-Hak KimDardinger Neuro-oncology Center, Department of Neurological Surgery, Ohio State University, Columbus, Ohio (T.H.K., J.S., S.-H.K., A.K.P., I.N., B.K., C.-H.K.); Solid Tumor Program at the James Comprehensive Cancer Center, Columbus, Ohio (T.H.K., J.S., A.K.P., C.-H.K.); Center for Biostatistics, Ohio State University, Columbus, Ohio (X.M.); Department of Radiation Oncology, Ohio State University, Columbus, Ohio (K.P.); Division of Hematology, Department of Internal Medicine, Ohio State University, Columbus, Ohio (J.Y.); Department of Molecular and Cellular Biochemistry, Ohio State University Wexner Medical Center, Columbus, Ohio (S.O.Y.).
Arav Krishnavadan ParikhDardinger Neuro-oncology Center, Department of Neurological Surgery, Ohio State University, Columbus, Ohio (T.H.K., J.S., S.-H.K., A.K.P., I.N., B.K., C.-H.K.); Solid Tumor Program at the James Comprehensive Cancer Center, Columbus, Ohio (T.H.K., J.S., A.K.P., C.-H.K.); Center for Biostatistics, Ohio State University, Columbus, Ohio (X.M.); Department of Radiation Oncology, Ohio State University, Columbus, Ohio (K.P.); Division of Hematology, Department of Internal Medicine, Ohio State University, Columbus, Ohio (J.Y.); Department of Molecular and Cellular Biochemistry, Ohio State University Wexner Medical Center, Columbus, Ohio (S.O.Y.).
Xiaokui MoDardinger Neuro-oncology Center, Department of Neurological Surgery, Ohio State University, Columbus, Ohio (T.H.K., J.S., S.-H.K., A.K.P., I.N., B.K., C.-H.K.); Solid Tumor Program at the James Comprehensive Cancer Center, Columbus, Ohio (T.H.K., J.S., A.K.P., C.-H.K.); Center for Biostatistics, Ohio State University, Columbus, Ohio (X.M.); Department of Radiation Oncology, Ohio State University, Columbus, Ohio (K.P.); Division of Hematology, Department of Internal Medicine, Ohio State University, Columbus, Ohio (J.Y.); Department of Molecular and Cellular Biochemistry, Ohio State University Wexner Medical Center, Columbus, Ohio (S.O.Y.).
Kamalakannan PalanichamyDardinger Neuro-oncology Center, Department of Neurological Surgery, Ohio State University, Columbus, Ohio (T.H.K., J.S., S.-H.K., A.K.P., I.N., B.K., C.-H.K.); Solid Tumor Program at the James Comprehensive Cancer Center, Columbus, Ohio (T.H.K., J.S., A.K.P., C.-H.K.); Center for Biostatistics, Ohio State University, Columbus, Ohio (X.M.); Department of Radiation Oncology, Ohio State University, Columbus, Ohio (K.P.); Division of Hematology, Department of Internal Medicine, Ohio State University, Columbus, Ohio (J.Y.); Department of Molecular and Cellular Biochemistry, Ohio State University Wexner Medical Center, Columbus, Ohio (S.O.Y.).
Balveen KaurDardinger Neuro-oncology Center, Department of Neurological Surgery, Ohio State University, Columbus, Ohio (T.H.K., J.S., S.-H.K., A.K.P., I.N., B.K., C.-H.K.); Solid Tumor Program at the James Comprehensive Cancer Center, Columbus, Ohio (T.H.K., J.S., A.K.P., C.-H.K.); Center for Biostatistics, Ohio State University, Columbus, Ohio (X.M.); Department of Radiation Oncology, Ohio State University, Columbus, Ohio (K.P.); Division of Hematology, Department of Internal Medicine, Ohio State University, Columbus, Ohio (J.Y.); Department of Molecular and Cellular Biochemistry, Ohio State University Wexner Medical Center, Columbus, Ohio (S.O.Y.).
Jianhua YuDardinger Neuro-oncology Center, Department of Neurological Surgery, Ohio State University, Columbus, Ohio (T.H.K., J.S., S.-H.K., A.K.P., I.N., B.K., C.-H.K.); Solid Tumor Program at the James Comprehensive Cancer Center, Columbus, Ohio (T.H.K., J.S., A.K.P., C.-H.K.); Center for Biostatistics, Ohio State University, Columbus, Ohio (X.M.); Department of Radiation Oncology, Ohio State University, Columbus, Ohio (K.P.); Division of Hematology, Department of Internal Medicine, Ohio State University, Columbus, Ohio (J.Y.); Department of Molecular and Cellular Biochemistry, Ohio State University Wexner Medical Center, Columbus, Ohio (S.O.Y.).
Sung Ok YoonDardinger Neuro-oncology Center, Department of Neurological Surgery, Ohio State University, Columbus, Ohio (T.H.K., J.S., S.-H.K., A.K.P., I.N., B.K., C.-H.K.); Solid Tumor Program at the James Comprehensive Cancer Center, Columbus, Ohio (T.H.K., J.S., A.K.P., C.-H.K.); Center for Biostatistics, Ohio State University, Columbus, Ohio (X.M.); Department of Radiation Oncology, Ohio State University, Columbus, Ohio (K.P.); Division of Hematology, Department of Internal Medicine, Ohio State University, Columbus, Ohio (J.Y.); Department of Molecular and Cellular Biochemistry, Ohio State University Wexner Medical Center, Columbus, Ohio (S.O.Y.).
Ichiro NakanoDardinger Neuro-oncology Center, Department of Neurological Surgery, Ohio State University, Columbus, Ohio (T.H.K., J.S., S.-H.K., A.K.P., I.N., B.K., C.-H.K.); Solid Tumor Program at the James Comprehensive Cancer Center, Columbus, Ohio (T.H.K., J.S., A.K.P., C.-H.K.); Center for Biostatistics, Ohio State University, Columbus, Ohio (X.M.); Department of Radiation Oncology, Ohio State University, Columbus, Ohio (K.P.); Division of Hematology, Department of Internal Medicine, Ohio State University, Columbus, Ohio (J.Y.); Department of Molecular and Cellular Biochemistry, Ohio State University Wexner Medical Center, Columbus, Ohio (S.O.Y.).
Chang-Hyuk KwonDardinger Neuro-oncology Center, Department of Neurological Surgery, Ohio State University, Columbus, Ohio (T.H.K., J.S., S.-H.K., A.K.P., I.N., B.K., C.-H.K.); Solid Tumor Program at the James Comprehensive Cancer Center, Columbus, Ohio (T.H.K., J.S., A.K.P., C.-H.K.); Center for Biostatistics, Ohio State University, Columbus, Ohio (X.M.); Department of Radiation Oncology, Ohio State University, Columbus, Ohio (K.P.); Division of Hematology, Department of Internal Medicine, Ohio State University, Columbus, Ohio (J.Y.); Department of Molecular and Cellular Biochemistry, Ohio State University Wexner Medical Center, Columbus, Ohio (S.O.Y.).
Neurological Surgery · USThe Ohio State University · USThe Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute · USThe Ohio State University Wexner Medical Center · US
Funding
The Tumor Microenvironmental Barrier to Effective Viral OncolysisP01CA163205 · NCI · OHIO STATE UNIVERSITY · PI MICHAEL A CALIGIURI · 2013 to 2026
$26.0MOhio State Neuroscience Centr CoreP30NS045758 · NINDS · OHIO STATE UNIVERSITY · PI OBRIETAN, KARL H · 2004 to 2015
$7.7MEnhancing Viral Oncolysis with Vasculostatin Gene DeliveryR01CA150153 · NCI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI KAUR, BALVEEN · 2011 to 2020
$4.0MOV Therapy Induced Changes in Tumor Secretome and Their Impact on TherapyR01NS064607 · NINDS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI KAUR, BALVEEN · 2008 to 2018
$3.2MElucidate and Modulate TGF-b Signaling in NK Cells for Glioma TreatmentR01CA155521 · NCI · OHIO STATE UNIVERSITY · PI YU, JIANHUA · 2012 to 2014
$921kNCI NIH HHS P01 CA163205NCI NIH HHS R01 CA150153NCI NIH HHS R01CA150153NCI NIH HHS R01 CA155521NINDS NIH HHS P30NS045758NINDS NIH HHS R01 NS064607NINDS NIH HHS R01NS064607
Abstract
backgroundsPiperlongumine, a natural plant product, kills multiple cancer types with little effect on normal cells. Piperlongumine raises intracellular levels of reactive oxygen species (ROS), a phenomenon that may underlie the cancer-cell killing. Although these findings suggest that piperlongumine could be useful for treating cancers, the mechanism by which the drug selectively kills cancer cells remains unknown.
methodsWe treated multiple high-grade glioma (HGG) sphere cultures with piperlongumine and assessed its effects on ROS and cell-growth levels as well as changes in downstream signaling. We also examined the levels of putative piperlongumine targets and their roles in HGG cell growth.
resultsPiperlongumine treatment increased ROS levels and preferentially killed HGG cells with little effect in normal brain cells. Piperlongumine reportedly increases ROS levels after interactions with several redox regulators. We found that HGG cells expressed higher levels of the putative piperlongumine targets than did normal neural stem cells (NSCs). Furthermore, piperlongumine treatment in HGG cells, but not in normal NSCs, increased oxidative inactivation of peroxiredoxin 4 (PRDX4), an ROS-reducing enzyme that is overexpressed in HGGs and facilitates proper protein folding in the endoplasmic reticulum (ER). Moreover, piperlongumine exacerbated intracellular ER stress, an effect that was mimicked by suppressing PRDX4 expression.
conclusionsOur results reveal that the mechanism by which piperlongumine preferentially kills HGG cells involves PRDX4 inactivation, thereby inducing ER stress. Therefore, piperlongumine treatment could be considered as a novel therapeutic option for HGG treatment.
Indexed as
AnimalsAntineoplastic AgentsApoptosisBrain NeoplasmsDatabases, FactualDioxolanesEndoplasmic Reticulum StressGliomaHumansMicePeroxiredoxinsPiperidonesReactive Oxygen SpeciesSurvival AnalysisTumor Cells, CulturedAntineoplastic AgentsDioxolanesPeroxiredoxinsPiperidonespiperlonguminePRDX4 protein, humanReactive Oxygen SpeciesEndoplasmic reticulum stresshigh-grade gliomaperoxiredoxin 4piperlonguminereactive oxygen species
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