ArticleOncoTargets and therapy2015
Micheliolide overcomes KLF4-mediated cisplatin resistance in breast cancer cells by downregulating glutathione.
Article in OncoTargets and therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Micheliolide and ACT001 as Covalent Modulators of Inflammation-Redox-Metabolism Networks in CNS Disorders: An Evidence-Stratified Review of Mechanisms and Translational Challenges.Drug design, development and therapy · 2026Review
- KLF4 in cancer chemoresistance: molecular mechanisms and therapeutic implications.Discover oncology · 2025Review
- Sesquiterpene lactones and cancer: new insight into antitumor and anti-inflammatory effects of parthenolide-derived Dimethylaminomicheliolide and Micheliolide.Frontiers in pharmacology · 2025Review
- KLF4: a multifunctional nexus connecting tumor progression and immune regulation.Frontiers in immunology · 2025Review
- Zinc Oxide Nanoparticles and Cancer Chemotherapy: Helpful Tools for Enhancing Chemo-sensitivity and Reducing Side Effects?Biological trace element research · 2024Review
- The antitumor effect of the novel agent MCL/ACT001 in pancreatic ductal adenocarcinoma.Journal of cancer research and clinical oncology · 2023Article
- Article
- Epigenetic-Metabolic Interplay in the DNA Damage Response and Therapeutic Resistance of Breast Cancer.Cancer research · 2023Article
- Nanoparticle-Mediated Delivery of Micheliolide Analogs to Eliminate Leukemic Stem Cells in the Bone Marrow.Advanced therapeutics · 2022Article
- Sesquiterpene Lactones and Cancer: New Insight into Antitumor and Anti-inflammatory Effects of Parthenolide-Derived Dimethylaminomicheliolide and Micheliolide.Computational and mathematical methods in medicine · 2022Review
- Antitumor effects of the small molecule DMAMCL in neuroblastoma via suppressing aerobic glycolysis and targeting PFKL.Cancer cell international · 2021Article
- Recent Discoveries on the Involvement of Krüppel-Like Factor 4 in the Most Common Cancer Types.International journal of molecular sciences · 2020Review
- Novel agent DMAMCL suppresses osteosarcoma growth and decreases the stemness of osteosarcoma stem cell.Cell cycle (Georgetown, Tex.) · 2020Article
- Cisplatin-resistant triple-negative breast cancer subtypes: multiple mechanisms of resistance.BMC cancer · 2019Article
- The anti-tumor growth effect of a novel agent DMAMCL in rhabdomyosarcoma in vitro and in vivo.Journal of experimental & clinical cancer research : CR · 2019Article
- KLF4, a miR-32-5p targeted gene, promotes cisplatin-induced apoptosis by upregulating BIK expression in prostate cancer.Cell communication and signaling : CCS · 2018Article
- Article
- N-[Bioorganic & medicinal chemistry letters · 2016Article
- Polysaccharide fromIranian journal of basic medical sciences · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Micheliolide (MCL) is a promising novel compound with broad-spectrum anticancer activity. However, little is known regarding its action and mechanism in breast cancer. To explore the potential therapeutic application of MCL as a chemosensitivity modulator, this study investigated the effects of MCL on cisplatin sensitivity in breast cancer and the underlying mechanisms. In the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxicity assay and a xenograft tumor model, MCL enhanced the cisplatin sensitivity of the breast cancer cell line MCF-7 both in vitro and in vivo. Treatment of MCF-7 cells with low-dose cisplatin (10 µM) was sufficient to enrich the proportion of ALDH(+) cells and upregulate Krüppel-like factor 4 (KLF4) expression. The results obtained from knockdown and overexpression experiments demonstrate that KLF4 is both necessary and sufficient to induce a cisplatin resistance phenotype in breast cancer cells. Furthermore, the glutathione (GSH) content was elevated in MCF-7 cells after overexpression of KLF4. KLF4-mediated resistance to cisplatin was found to be abrogated by treatment with buthionine sulfoximine, an inhibitor of GSH synthesis. MCL induced GSH depletion and severe cell death in KLF4-overexpressing MCF-7 cells following exposure to cisplatin. Therefore, these results suggest that MCL-mediated direct depletion of GSH represents a major mechanism in reversing KLF4-induced cisplatin resistance in MCF-7 cells.
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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.