ArticleBritish journal of pharmacology2017
Tetrandrine antagonizes acute megakaryoblastic leukaemia growth by forcing autophagy-mediated differentiation.
Article in British journal of pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 38 citations in OpenAlex.
- Novel perceptions and insights into the rare hematologic malignancy of acute megakaryocytic leukemia: a multicenter clinical retrospective study.Frontiers in medicine · 2025Article
- Tetrandrine induces muscle atrophy involving ROS-mediated inhibition of Akt and FoxO3.Molecular medicine (Cambridge, Mass.) · 2024Article
- Article
- Tetrandrine Inhibits Skeletal Muscle Differentiation by Blocking Autophagic Flux.International journal of molecular sciences · 2022Article
- Tetrandrine Ameliorates Traumatic Brain Injury by Regulating Autophagy to Reduce Ferroptosis.Neurochemical research · 2022Article
- Progress on structural modification of Tetrandrine with wide range of pharmacological activities.Frontiers in pharmacology · 2022Review
- Targeting the two-pore channel 2 in cancer progression and metastasis.Exploration of targeted anti-tumor therapy · 2022Review
- Deregulated calcium signaling in blood cancer: Underlying mechanisms and therapeutic potential.Frontiers in oncology · 2022Review
- Tetrandrine Modulates Rheb-mTOR Signaling-Mediated Selective Autophagy and Protects Pulmonary Fibrosis.Frontiers in pharmacology · 2021Article
- Design, Synthesis of Novel Tetrandrine-14-l-Amino Acid and Tetrandrine-14-l-Amino Acid-Urea Derivatives as Potential Anti-Cancer Agents.Molecules (Basel, Switzerland) · 2020Article
- A critical review: traditional uses, phytochemistry, pharmacology and toxicology ofPhytochemistry reviews : proceedings of the Phytochemical Society of Europe · 2020Review
- Tetrandrine Prevents Bone Loss in Ovariectomized Mice by Inhibiting RANKL-Induced Osteoclastogenesis.Frontiers in pharmacology · 2019Article
- Targeting Reactive Oxygen Species in Cancer via Chinese Herbal Medicine.Oxidative medicine and cellular longevity · 2019Review
- Combination therapy with protein kinase inhibitor H89 and Tetrandrine elicits enhanced synergistic antitumor efficacy.Journal of experimental & clinical cancer research : CR · 2018Article
- Tetrandrine antagonizes acute megakaryoblastic leukaemia growth by forcing autophagy-mediated differentiation.British journal of pharmacology · 2017Article
- Design, Synthesis and Anticancer Evaluation of Fangchinoline Derivatives.Molecules (Basel, Switzerland) · 2017Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe poor prognosis of acute megakaryoblastic leukaemia (AMKL) means there is a need to develop novel therapeutic methods to treat this condition. It was recently shown that inducing megakaryoblasts to undergo terminal differentiation is effective as a treatment for AMKL. This encouraged us to identify a compound that induces megakaryocyte differentiation, which could then act as a potent anti-leukaemia agent. EXPERIMENTAL APPROACH: The effects of tetrandrine on the expression of CD41 and cell morphology were investigated in AMKL cells. We used CRISPR/Cas9 knockout system to knock out ATG7 and verify the role of autophagy in tetrandrine-induced megakaryocyte differentiation. shNotch1 and CA-Akt were transfected into K562 cells to examine the downstream pathways of ROS signalling and the mechanistic basis of the tetrandrine-induced megakaryocyte differentiation. The anti-leukaemia effects of tetrandrine were analysed both in vitro and in vivo. KEY
resultsA low dose of tetrandrine induced cell cycle arrest and megakaryocyte differentiation in AMKL cells via activation of autophagy. Molecularly, we demonstrated that this effect is mediated by activation of Notch1 and Akt and subsequent accumulation of ROS. In contrast, in normal mouse fetal liver cells, although tetrandrine induced autophagy, it did not affect cell proliferation or promote megakaryocyte differentiation, suggesting a specific effect of tetrandrine in malignant megakaryoblasts. Finally, tetrandrine also showed in vivo efficacy in an AMKL xenograft mouse model. CONCLUSIONS AND IMPLICATIONS: Modulating autophagy-mediated differentiation may be a novel strategy for treating AMKL, and tetrandrine has the potential to be developed as a differentiation-inducing agent for AMKL chemotherapy.
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