ArticleThe Journal of biological chemistry2016
Targeting Thioredoxin Reductase by Parthenolide Contributes to Inducing Apoptosis of HeLa Cells.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 123 citations in OpenAlex.
- Selenoproteins: Minute yet vital players governing cellular fate.Genes & diseases · 2026Review
- Context‑dependent targeting of thioredoxin reductase 1 in cancer: a mechanistic review.Magyar onkologia · 2026Review
- Identification of Novel JAK2 Inhibitors from Amino Derivatives of Epoxyalantolactone: In Silico and In Vitro Studies.International journal of molecular sciences · 2025Article
- Purification, Fluorescent Labeling, and Detyrosination of Mammalian Cell Tubulin for Biochemical Assays.Cytoskeleton (Hoboken, N.J.) · 2025Article
- The Dual Role of Dietary Phytochemicals in Oxidative Stress: Implications for Oncogenesis, Cancer Chemoprevention, and ncRNA Regulation.Antioxidants (Basel, Switzerland) · 2025Review
- Pharmacological Inhibition of TXNRD1 by a Small Molecule Flavonoid Butein Overcomes Cisplatin Resistance in Lung Cancer Cells.Biological trace element research · 2025Article
- Parthenolide Inhibits Tumor Cell Growth and Metastasis in Melanoma A2058 Cells.Current medicinal chemistry · 2025Article
- Research advances in natural sesquiterpene lactones: overcoming cancer drug resistance through modulation of key signaling pathways.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Gold complex QB1561 suppresses drug-resistant cancer cells by inhibiting TrxR and mitochondrial respiratory function.Frontiers in pharmacology · 2025Article
- Natural products for enhancing the sensitivity or decreasing the adverse effects of anticancer drugs through regulating the redox balance.Chinese medicine · 2024Review
- Parthenolide As a Therapeutic for Disseminated Canine Neoplasms.The Journal of pharmacology and experimental therapeutics · 2024Article
- Sesquiterpene lactones as emerging biomolecules to cease cancer by targeting apoptosis.Frontiers in pharmacology · 2024Review
- Benzophenanthridine Alkaloid Chelerythrine Elicits Necroptosis of Gastric Cancer Cells via Selective Conjugation at the Redox Hyperreactive C-Terminal SecMolecules (Basel, Switzerland) · 2023Article
- Heterocyclic Iminoquinones and Quinones from the National Cancer Institute (NCI, USA) COMPARE Analysis.Molecules (Basel, Switzerland) · 2023Review
- Ferroptosis-modulating small molecules for targeting drug-resistant cancer: Challenges and opportunities in manipulating redox signaling.Medicinal research reviews · 2023Review
- Disequilibrium in the Thioredoxin Reductase-1/Thioredoxin-1 Redox Couple Is Associated with Increased T-Cell Apoptosis in Children with Autism.Metabolites · 2023Article
- Synthesis and Anticancer Potential of New Hydroxamic Acid Derivatives as Chemotherapeutic Agents.Applied biochemistry and biotechnology · 2022Article
- Developing Bi-Gold Compound BGC2a to Target Mitochondria for the Elimination of Cancer Cells.International journal of molecular sciences · 2022Article
- Parthenolide and Its Soluble Analogues: Multitasking Compounds with Antitumor Properties.Biomedicines · 2022Review
- The Emerging Potential of Parthenolide Nanoformulations in Tumor Therapy.Drug design, development and therapy · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parthenolide (PTL), a major active sesquiterpene lactone from the herbal plant Tanacetum parthenium, has been applied in traditional Chinese medicine for centuries. Although PTL demonstrates potent anticancer efficacy in numerous types of malignant cells, the cellular targets of PTL have not been well defined. We reported here that PTL interacts with both cytosolic thioredoxin reductase (TrxR1) and mitochondrial thioredoxin reductase (TrxR2), two ubiquitous selenocysteine-containing antioxidant enzymes, to elicit reactive oxygen species-mediated apoptosis in HeLa cells. PTL selectively targets the selenocysteine residue in TrxR1 to inhibit the enzyme function, and further shifts the enzyme to an NADPH oxidase to generate superoxide anions, leading to reactive oxygen species accumulation and oxidized thioredoxin. Under the conditions of inhibition of TrxRs in cells, PTL does not cause significant alteration of cellular thiol homeostasis, supporting selective target of TrxRs by PTL. Importantly, overexpression of functional TrxR1 or Trx1 confers protection, whereas knockdown of the enzymes sensitizes cells to PTL treatment. Targeting TrxRs by PTL thus discloses an unprecedented mechanism underlying the biological activity of PTL, and provides deep insights to understand the action of PTL in treatment of cancer.
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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.