ArticleBlood cancer journal2014
Nimbolide targets BCL2 and induces apoptosis in preclinical models of Waldenströms macroglobulinemia.
Article in Blood cancer journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 31 citations in OpenAlex.
- Nimbolide: A Potential Phytochemical Agent in Multimodal Pancreatic Cancer Therapies.Mini reviews in medicinal chemistry · 2025Review
- Exploring the therapeutic potential of Neem (Annals of translational medicine · 2022Review
- A Virtual Screening Platform Identifies Chloroethylagelastatin A as a Potential Ribosomal Inhibitor.Biomolecules · 2020Article
- Nanodelivery and anticancer effect of a limonoid, nimbolide, in breast and pancreatic cancer cells.International journal of nanomedicine · 2019Article
- Tracing the biosynthetic origin of limonoids and their functional groups through stable isotope labeling and inhibition in neem tree (Azadirachta indica) cell suspension.BMC plant biology · 2018Article
- Targeting CD38 with daratumumab is lethal to Waldenström macroglobulinaemia cells.British journal of haematology · 2018Article
- DnaJ homolog subfamily A member1 (DnaJ1) is a newly discovered anti-apoptotic protein regulated by azadirachtin in Sf9 cells.BMC genomics · 2018Article
- Waldenstrom macroglobulinemia cells devoid of BTKBlood cancer journal · 2017Article
- Coinhibition of the deubiquitinating enzymes, USP14 and UCHL5, with VLX1570 is lethal to ibrutinib- or bortezomib-resistant Waldenstrom macroglobulinemia tumor cells.Blood cancer journal · 2016Article
- Anticancer properties of nimbolide and pharmacokinetic considerations to accelerate its development.Oncotarget · 2016Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neem leaf extract (NLE) has medicinal properties, which have been attributed to its limonoid content. We identified the NLE tetranorterpenoid, nimbolide, as being the key limonoid responsible for the cytotoxicity of NLE in various preclinical models of human B-lymphocyte cancer. Of the models tested, Waldenströms macroglobulinemia (WM) cells were most sensitive to nimbolide, undergoing significant mitochondrial mediated apoptosis. Notably, nimbolide toxicity was also observed in drug-resistant (bortezomib or ibrutinib) WM cells. To identify putative targets of nimbolide, relevant in WM, we used chemoinformatics-based approaches comprised of virtual in silico screening, molecular modeling and target-ligand reverse docking. In silico analysis revealed the antiapoptotic protein BCL2 was the preferential binding partner of nimbolide. The significance of this finding was further tested in vitro in RS4;11 (BCL2-dependent) tumor cells, in which nimbolide induced significantly more apoptosis compared with BCL2 mutated (Jurkat BCL2(Ser70-Ala)) cells. Lastly, intraperitoneal administration of nimbolide in WM tumor xenografted mice, significantly reduced tumor growth and IgM secretion in vivo, while modulating the expression of several proteins as seen on immunohistochemistry. Overall, our data demonstrate that nimbolide is highly active in WM cells, as well as other B-cell cancers, and engages BCL2 to exert its cytotoxic activity.
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