ArticleCancer biology & therapy2012
Oridonin in combination with imatinib exerts synergetic anti-leukemia effect in Ph+ acute lymphoblastic leukemia cells in vitro by inhibiting activation of LYN/mTOR signaling pathway.
Article in Cancer biology & therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 47 citations in OpenAlex.
- Natural Products Targeting BCR-ABL: A Plant-Based Approach to Chronic Myeloid Leukemia Treatment.Molecules (Basel, Switzerland) · 2025Review
- Research and Development Progression of Oridonin for Hematological Malignancies Therapy.Current medicinal chemistry · 2025Review
- Molecular Secrets Revealed: How Diabetes may be Paving the Way for Leukemia.Current treatment options in oncology · 2024Review
- Oridonin fromFood science & nutrition · 2024Review
- High cystic fibrosis transmembrane conductance regulator expression in childhood B-cell acute lymphoblastic leukemia acts as a potential therapeutic target.Translational cancer research · 2022Article
- Oridonin and its derivatives for cancer treatment and overcoming therapeutic resistance.Genes & diseases · 2021Review
- Leukemic cells expressing NCOR1-LYN are sensitive to dasatinib in vivo in a patient-derived xenograft mouse model.Leukemia · 2021Article
- RanBP3 Regulates Proliferation, Apoptosis and Chemosensitivity of Chronic Myeloid Leukemia CellsFrontiers in oncology · 2021Article
- Oridonin enhances the anti-tumor activity of gemcitabine towards pancreatic cancer by stimulating Bax- and Smac-dependent apoptosis.Translational cancer research · 2020Article
- Synergistic killing effects of homoharringtonine and arsenic trioxide on acute myeloid leukemia stem cells and the underlying mechanisms.Journal of experimental & clinical cancer research : CR · 2019Article
- Oridonin overcomes the gemcitabine resistant PANC-1/Gem cells by regulating GST pi and LRP/1 ERK/JNK signalling.OncoTargets and therapy · 2019Article
- Protective Effects of Oridonin on Acute Liver Injury via Impeding Posttranslational Modifications of Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) in the Toll-Like Receptor 4 (TLR4) Signaling Pathway.Mediators of inflammation · 2019Article
- Oridonin Enhances Radiation-Induced Cell Death by Promoting DNA Damage in Non-Small Cell Lung Cancer Cells.International journal of molecular sciences · 2018Article
- Role of Non Receptor Tyrosine Kinases in Hematological Malignances and its Targeting by Natural Products.Molecular cancer · 2018Review
- [Oridonin inhibits proliferation of Jurkat cells via the down-regulation of Brg1].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2017Article
- Oridonin inhibits pancreatic cancer cell migration and epithelial-mesenchymal transition by suppressing Wnt/β-catenin signaling pathway.Cancer cell international · 2016Article
- Synergistic anticancer effects of combined γ-tocotrienol and oridonin treatment is associated with the induction of autophagy.Molecular and cellular biochemistry · 2015Article
- Molecular Insight in the Multifunctional Effects of Oridonin.Drugs in R&D · 2015Review
- Article
- Selective anti-cancer agents as anti-aging drugs.Cancer biology & therapy · 2013Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is triggered by constitutively activated BCR-ABL and SRC family tyrosine kinases.They account for the activations of multiple growth-signaling pathways, including Raf/MEK/ERK, Akt/mTOR and STAT5 pathways. The BCR-ABL tyrosine kinase inhibitor imatinib is the standard treatment for Ph+ leukemia and plays efficacious role in CML. However, imatinib has few inhibitory effects on SRC tyrosine kinase with response rate of Ph+ ALL lower and relapse more frequent and quicker compared with CML. Previous studies showed that oridonin inhibits proliferation and induces apoptosis in many tumor cells. However, the anticancer activity and mechanism of oridonin in Ph+ ALL is unknown. To investigate the anticancer activity of oridonin, we examined its role in constitutively activated Akt/mTOR, Raf/MEK/ERK, STAT5 and SRC pathway, mRNA level of bcr/abl gene, cell viability and apoptosis in Ph+ ALL SUP-B15 cells. Furthermore, we detected synergetic effect of oridonin plus imatinib. Our results showed that oridonin inhibiting activations of LYN (one of SRC family kinases) and ABL and their downstream Akt/mTOR, Raf/MEK/ERK and STAT5 pathways, downregulated Bcl-2 but upregulated Bax protein and then induced apoptosis in Ph+ ALL cells. Oridonin plus imatinib exerted synergetic effects by overcoming imatinib defect of upregulating Akt/mTOR and LYN signaling. Additionally, we examined the effect of oridonin on the signaling pathways in the primary specimens from Ph+ ALL patients. Our data showed that oridonin remarkably suppressed activations of Akt/mTOR, Raf/MEK and STAT5 pathway in these primary specimens and oridonin with imatinib exerted synergetic suppressive effects on mTOR, STAT5 and LYN signaling in one imatinib resistant patient specimen. Additional evaluation of oridonin as a potential therapeutic agent for Ph+ ALL seems warranted.
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