ArticleCell death & disease2020
Combining triptolide with ABT-199 is effective against acute myeloid leukemia through reciprocal regulation of Bcl-2 family proteins and activation of the intrinsic apoptotic pathway.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Triptolide: A Narrative Review of Its Traditional Use, Derivatives, Pharmacology, Antitumor Effect, and Clinical Applications.Cancers · 2026Review
- Dual targeting of PI3Kδ and PPARα enhances antitumor activity via FoxO1 activation in follicular lymphoma.Cell death & disease · 2026Article
- Pleiotropic pharmacological activities and multiple-organ toxicities of triptolide: a programmed cell death perspective.Chinese medicine · 2026Review
- Synergistic anti-hepatoma effect of triptolide and quercetinWorld journal of gastroenterology · 2026Article
- Phytochemicals in overcoming venetoclax resistance in acute myeloid leukemia: mechanistic insights and therapeutic potential.Annals of hematology · 2025Review
- The synergy of TPL and selinexor in MLL-R acute myeloid leukemia via Rap1/Raf/MEK pathway-mediated MYC downregulation.Translational oncology · 2025Article
- Natural anti-cancer products: insights from herbal medicine.Chinese medicine · 2025Review
- Progressive lung fibrosis: reprogramming a genetically vulnerable bronchoalveolar epithelium.The Journal of clinical investigation · 2025Review
- Triptolide induces apoptosis of glioma cells by inhibiting NF-κB activation during oxidative stress.Scientific reports · 2024Article
- Review
- Increased MCL1 dependency leads to new applications of BH3-mimetics in drug-resistant neuroblastoma.British journal of cancer · 2023Article
- Bcl-2 inhibition combined with PPARα activation synergistically targets leukemic stem cell-like cells in acute myeloid leukemia.Cell death & disease · 2023Article
- Therapeutic synergy of Triptolide and MDM2 inhibitor against acute myeloid leukemia through modulation of p53-dependent and -independent pathways.Experimental hematology & oncology · 2022Article
- BH3-mimetics: recent developments in cancer therapy.Journal of experimental & clinical cancer research : CR · 2021Review
- MYC2 Transcription Factors TwMYC2a and TwMYC2b Negatively Regulate Triptolide Biosynthesis inPlants (Basel, Switzerland) · 2021Article
- Isolation and Functional Characterization of the Promoters of Miltiradiene Synthase Genes,Plants (Basel, Switzerland) · 2021Article
- Effects of Qinghuang Powder on Acute Myeloid Leukemia Based on Network Pharmacology, Molecular Docking, and In Vitro Experiments.Evidence-based complementary and alternative medicine : eCAM · 2021Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bcl-2 inhibitors display an effective activity in acute myeloid leukemia (AML), but its clinical efficacy as a monotherapy was limited in part owing to failure to target other antiapoptotic Bcl-2 family proteins, such as Mcl-1. In this context, the combination strategy may be a promising approach to overcome this barrier. Here, we report the preclinical efficacy of a novel strategy combining ABT-199 with triptolide (TPL), a natural product extracted from a traditional Chinese medicine, in AML. Combination treatment exhibited markedly increased cytotoxicity in leukemic cells irrespective of p53 status while largely sparing normal cells of the hematopoietic lineage. Moreover, co-administration of ABT-199 with TPL dramatically suppressed leukemia progression as well as prolonged animal survival in a xenograft AML model. The potentiated effect of ABT-199 and TPL against AML was associated with activation of the mitochondrum-related intrinsic apoptotic pathway through a mechanism reciprocally modulating Bcl-2 family proteins. In this case, TPL not only downregulated Mcl-1 but also upregulated proapoptotic BH3-only proteins, thereby overcoming the resistance toward ABT-199. Conversely, ABT-199 abrogated Bcl-2-mediated cytoprotection against TPL. Together, these findings suggest that the regimen combining TPL and ABT-199 might be active against AML by inducing robust apoptosis through reciprocal regulation of anti- and proapoptotic Bcl-2 family proteins, therefore providing a strong rationale for the clinical investigation of this combination regimen for the treatment of AML.
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