ArticleCell death & disease2016
The clerodane diterpene casearin J induces apoptosis of T-ALL cells through SERCA inhibition, oxidative stress, and interference with Notch1 signaling.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- The dynamic equilibrium between the protective and toxic effects of matrine in the development of liver injury: a systematic review and meta-analysis.Frontiers in pharmacology · 2024Pooled it
- The Protective Effect of Nimodipine in Schwann Cells Is Related to the Upregulation of LMO4 and SERCA3 Accompanied by the Fine-Tuning of Intracellular Calcium Levels.International journal of molecular sciences · 2025Article
- Notch Inhibitors and BH3 Mimetics in T-Cell Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2024Review
- Modulation of Notch Signaling by Small-Molecular Compounds and Its Potential in Anticancer Studies.Cancers · 2023Review
- Advances on Natural Abietane, Labdane and Clerodane Diterpenes as Anti-Cancer Agents: Sources and Mechanisms of Action.Molecules (Basel, Switzerland) · 2022Review
- Inhibition of mitochondrial complex I reverses NOTCH1-driven metabolic reprogramming in T-cell acute lymphoblastic leukemia.Nature communications · 2022Article
- Deregulated calcium signaling in blood cancer: Underlying mechanisms and therapeutic potential.Frontiers in oncology · 2022Review
- Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives.Cancers · 2021Review
- Clinical significance of P-class pumps in cancer.Oncology letters · 2021Review
- Targeting oncogenic Notch signaling with SERCA inhibitors.Journal of hematology & oncology · 2021Review
- From Plant to Patient: Thapsigargin, a Tool for Understanding Natural Product Chemistry, Total Syntheses, Biosynthesis, Taxonomy, ATPases, Cell Death, and Drug Development.Progress in the chemistry of organic natural products · 2021Article
- Hugan Qingzhi medication ameliorates free fatty acid-induced L02 hepatocyte endoplasmic reticulum stress by regulating the activation of PKC-δ.BMC complementary medicine and therapies · 2020Article
- Advances of target therapy on NOTCH1 signaling pathway in T-cell acute lymphoblastic leukemia.Experimental hematology & oncology · 2020Review
- Review
- Blockade of Oncogenic NOTCH1 with the SERCA Inhibitor CAD204520 in T Cell Acute Lymphoblastic Leukemia.Cell chemical biology · 2020Article
- Endoplasmic Reticulum Calcium Pumps and Tumor Cell Differentiation.International journal of molecular sciences · 2020Review
- Metformin relieves neuropathic pain after spinal nerve ligation via autophagy flux stimulation.Journal of cellular and molecular medicine · 2019Article
- Melatonin protects vertebral endplate chondrocytes against apoptosis and calcification via the Sirt1-autophagy pathway.Journal of cellular and molecular medicine · 2019Article
- Therapeutic Targeting of Notch Signaling Pathway in Hematological Malignancies.Mediterranean journal of hematology and infectious diseases · 2019Review
- Bepridil exhibits anti-leukemic activity associated with NOTCH1 pathway inhibition in chronic lymphocytic leukemia.International journal of cancer · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy that preferentially affects children and adolescents. Over 50% of human T-ALLs possess activating mutations of Notch1. The clerodane diterpene casearin J (CJ) is a natural product that inhibits the sarcoendoplasmatic reticulum calcium ATPase (SERCA) pump and induces cell death in leukemia cells, but the molecular mechanism of cytotoxicity remains poorly understood. Here we show that owing to SERCA pump inhibition, CJ induces depletion of the endoplasmic reticulum calcium pools, oxidative stress, and apoptosis via the intrinsic signaling pathway. Moreover, Notch1 signaling is reduced in T-ALL cells with auto-activating mutations in the HD-domain of Notch1, but not in cells that do not depend on Notch1 signaling. CJ also provoked a slight activation of NF-κB, and consistent with this notion a combined treatment of CJ and the NF-κB inhibitor parthenolide (Pt) led to a remarkable synergistic cell death in T-ALL cells. Altogether, our data support the concept that inhibition of the SERCA pump may be a novel strategy for the treatment of T-ALL with HD-domain-mutant Notch1 receptors and that additional treatment with the NF-κB inhibitor parthenolide may have further therapeutic benefits.
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