ArticleMolecular medicine reports2023
Triptolide promotes ferroptosis by suppressing Nrf2 to overcome leukemia cell resistance to doxorubicin.
Article in Molecular medicine reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Ferroptosis research based on bibliometric and visual analysis: mechanism exploration and clinical application prospects in gastric cancer, prostate cancer, leukemia, and brain tumors.Frontiers in medicine · 2025Pooled it
- Recent advancements in NRF2-regulated ferroptosis modulation for targeted cancer therapy.Molecular biology reports · 2026Review
- Pleiotropic pharmacological activities and multiple-organ toxicities of triptolide: a programmed cell death perspective.Chinese medicine · 2026Review
- Targeting Galectin-1 with Triptolide Induces Ferroptosis in Oral Squamous Cell Carcinoma.Cancers · 2026Article
- Targeting Ferroptosis to Overcome Drug Resistance in Cancer: Molecular Mechanisms and Therapeutic Prospects.Biomolecules & therapeutics · 2026Review
- Article
- Triptolide-mediated immunomodulation of macrophages: from pathophysiology to therapy.Annals of medicine · 2025Review
- Naturally Derived SENP1 Inhibitors with Anticancer Activity.International journal of molecular sciences · 2025Review
- Potential of Apigenin, Berberine, Chrysin, and Luteolin to Overcome Doxorubicin Resistance in Acute Promyelocytic Leukemia HL-60 Cells.International journal of molecular sciences · 2025Article
- Targeting Nrf2 in acute myeloid leukemia: an updated review on its role in chemoresistance and emerging therapeutic strategies.Medical oncology (Northwood, London, England) · 2025Review
- Co‑treatment with triptolide and RSL3 induces hepatocellular carcinoma cell apoptosis and ferroptosis.Molecular medicine reports · 2025Article
- Natural anti-cancer products: insights from herbal medicine.Chinese medicine · 2025Review
- Review
- Crocin promotes ferroptosis in gastric cancer via the Nrf2/GGTLC2 pathway.Frontiers in pharmacology · 2025Article
- A comprehensive overview of triptolide utilizing nanotechnology and its potential applications in prostate diseases.Frontiers in pharmacology · 2025Review
- The regulation and function of Nrf2 signaling in ferroptosis-activated cancer therapy.Acta pharmacologica Sinica · 2024Review
- Potential of NRF2 Inhibitors-Retinoic Acid, K67, and ML-385-In Overcoming Doxorubicin Resistance in Promyelocytic Leukemia Cells.International journal of molecular sciences · 2024Article
- Therapeutic Potential of Terpenoids in Cancer Treatment: Targeting Mitochondrial Pathways.Cancer reports (Hoboken, N.J.) · 2024Review
- Antitumor mechanisms and future clinical applications of the natural product triptolide.Cancer cell international · 2024Review
- Disulfide Cross-Linked Polymeric Redox-Responsive Nanocarrier Based on Heparin, Chitosan and Lipoic Acid Improved Drug Accumulation, Increased Cytotoxicity and Selectivity to Leukemia Cells by Tumor Targeting via "Aikido" Principle.Gels (Basel, Switzerland) · 2024Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Doxorubicin (DOX) is an extensively used chemotherapeutic drug to treat leukemia. However, there remains a pivotal clinical problem of resistance to DOX in patients with leukemia. Erythroid 2‑related factor 2 (Nrf2) is a master regulator of antioxidation response which serves a critical role in maintaining cellular oxidative homeostasis. However, whether Nrf2 is involved in DOX resistance is not totally clear. It is well‑documented that triptolide, a widely used drug to treat autoimmune disorders, possesses anti‑cancer activities, yet whether triptolide affects leukemia cell sensitivity to DOX remains to be elucidated. The present study aimed to determine the role of triptolide‑mediated downregulation of Nrf2 in regulating leukemia cell ferroptosis and resistance to DOX. For this purpose, low‑dose DOX was used to establish DOX‑resistant K562 cells and HL‑60 cells. Nrf2 mRNA and protein expression were examined by quantitative PCR and western blotting assays. The effects of triptolide on leukemia cell viability, reactive oxygen species (ROS) levels, or lipid oxidation were determined by CCK8 assay, DCFH‑DA assay, or BODIPY 581/591 C11 assay, respectively. The results show that Nrf2 expression was significantly upregulated in DOX‑resistant leukemia cells and clinical leukemia samples. Silencing of Nrf2 significantly sensitized leukemia cells to DOX. Furthermore, it was demonstrated that triptolide inhibited Nrf2 expression and induced leukemia cell ferroptosis, as evidenced by increased ROS levels and lipid oxidation as well as decreased glutathione peroxidase 4 expression. Ectopic expression of Nrf2 significantly rescued triptolide‑induced leukemia cell ferroptosis. Notably, the present study showed that triptolide re‑sensitized DOX‑resistant leukemia cells to DOX. In conclusion, the present study indicated that Nrf2 served a critical role in leukemia cell resistance to DOX and triptolide‑induced ferroptosis and suggested a potential strategy of combination therapy using triptolide and DOX in leukemia treatment.
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