ArticleActa pharmacologica Sinica2014
Oridonin induces NPM mutant protein translocation and apoptosis in NPM1c+ acute myeloid leukemia cells in vitro.
Article in Acta pharmacologica Sinica, 2014. 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, 33 citations in OpenAlex.
- Research and Development Progression of Oridonin for Hematological Malignancies Therapy.Current medicinal chemistry · 2025Review
- The nuclear export protein exportin-1 in solid malignant tumours: From biology to clinical trials.Clinical and translational medicine · 2024Review
- Oridonin fromFood science & nutrition · 2024Review
- Novel-and Not So Novel-Inhibitors of the Multifunctional CRM1 Protein.Oncology reviews · 2024Review
- Oridonin inhibits DNMT3A R882 mutation-driven clonal hematopoiesis and leukemia by inducing apoptosis and necroptosis.Cell death discovery · 2021Article
- Oridonin ameliorates inflammation-induced bone loss in mice via suppressing DC-STAMP expression.Acta pharmacologica Sinica · 2021Article
- Pseudolaric acid B induces apoptosis in human rhabdomyosarcoma RD cells.Oncology letters · 2020Article
- Nucleophosmin in Its Interaction with Ligands.International journal of molecular sciences · 2020Review
- Engineering chromosome region maintenance 1 fragments that bind to nuclear export signals.Protein science : a publication of the Protein Society · 2020Article
- Potential Applications of NRF2 Modulators in Cancer Therapy.Antioxidants (Basel, Switzerland) · 2020Review
- Mechanistic Pathways and Molecular Targets of Plant-Derived AnticancerBiomolecules · 2020Review
- Small Molecule Inhibitors of CRM1.Frontiers in pharmacology · 2020Review
- Oridonin induces Mdm2-p60 to promote p53-mediated apoptosis and cell cycle arrest in neuroblastoma.Cancer medicine · 2019Article
- Oridonin exerts anticancer effect on osteosarcoma by activating PPAR-γ and inhibiting Nrf2 pathway.Cell death & disease · 2018Article
- Pseudolaric acid B induced autophagy, but not apoptosis, in MRC5 human fibroblast cells.Oncology letters · 2018Article
- Conformational stabilization as a strategy to prevent nucleophosmin mislocalization in leukemia.Scientific reports · 2017Article
- Mechanisms of inhibiting human leukemia cell lines by serum of rats treated with compound banmao capsule.Oncology letters · 2017Article
- Pseudolaric acid B inhibits proliferation in SW579 human thyroid squamous cell carcinoma.Molecular medicine reports · 2015Article
- Inhibiting cancer cell hallmark features through nuclear export inhibition.Signal transduction and targeted therapyReview
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimSkewed cytoplasmic accumulation of NPM mutant protein (NPM1c+) is close related to leukemia pathogenesis. The aim of this study was to investigate whether oridonin, a diterpenoid isolated from the Chinese traditional medicine Rabdosia rubescens, was able to interfere with NPM1c+ protein trafficking and induce apoptosis in NPM1c+ acute myeloid leukemia cells in vitro.
methodsOCI-AML3 cell line harboring a NPM1 gene mutation was examined. Cell growth was detected by MTT assay. Cell apoptosis was evaluated using flow cytometry and Hoechst 33258 staining. The expression and subcellular localization of relevant proteins were detected by Western blot and immunofluorescent staining. The mRNA expression was detected by RT-PCR.
resultsOridonin (2-12 μmol/L) dose-dependently inhibited the viability of OCI-AML3 cells (the IC50 value was 3.27±0.23 μmol/L at 24 h). Moreover, oridonin induced OCI-AML3 cell apoptosis accompanied by activation of caspase-3 and nuclear translocation of NPM1c+ protein. Oridonin did not change the expression of Crm1 (the export receptor for nuclear export signal-containing proteins), but induced nuclear translocation of Crm1. Oridonin markedly increased the expression of nucleoporin98 (Nup98), which had an important role in Crm1-mediated nuclear protein export, and induced nuclear accumulation of Nup98. Furthermore, oridonin markedly increased the expression of p14arf and p53.
conclusionIn NPM1c+ leukemia cells, oridonin induces NPM1c+ protein translocation into the nucleus possibly via nuclear accumulation of Crm1; the compound markedly increases p53 and p14arf expression, which may contribute to cell apoptosis.
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