ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Gambogic acid induces apoptosis in imatinib-resistant chronic myeloid leukemia cells via inducing proteasome inhibition and caspase-dependent Bcr-Abl downregulation.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 129 citations in OpenAlex.
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- The Role of Nutraceuticals in Chemoprevention and their Therapeutic Effects when used in Combination with Synthetic Drugs.Current medicinal chemistry · 2025Review
- Antitumor effects and mechanisms of traditional Chinese medicine gamboge: A review.Frontiers in pharmacology · 2025Review
- Multi-targeted pharmacological actions and nanodelivery strategies of Garcinia cambogia: from molecular mechanisms to disease treatment.Frontiers in chemistry · 2025Review
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- Emerging tendencies for the nano-delivery of gambogic acid: a promising approach in oncotherapy.RSC advances · 2024Review
- Bioactive Phytoconstituents and Their Therapeutic Potentials in the Treatment of Haematological Cancers: A Review.Life (Basel, Switzerland) · 2023Review
- Isoalantolactone mediates the degradation of BCR-ABL protein in imatinib-resistant CML cells by down-regulating survivin.Cell cycle (Georgetown, Tex.) · 2023Article
- Evolution of Natural Product Scaffolds as Potential Proteasome Inhibitors in Developing Cancer Therapeutics.Metabolites · 2023Review
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- Inhibition of proteasomal deubiquitinases USP14 and UCHL5 overcomes tyrosine kinase inhibitor resistance in chronic myeloid leukaemia.Clinical and translational medicine · 2022Article
- Epigenetic DNA methylation of Zbtb7b regulates the population of double-positive CD4Journal of translational medicine · 2022Article
- Research Progress of Natural Small-Molecule Compounds Related to Tumor Differentiation.Molecules (Basel, Switzerland) · 2022Review
- Pterostilbene downregulates BCR/ABL and induces apoptosis of T315I-mutated BCR/ABL-positive leukemic cells.Scientific reports · 2022Article
- Fucoxanthin prevents breast cancer metastasis by interrupting circulating tumor cells adhesion and transendothelial migration.Frontiers in pharmacology · 2022Article
- Suppression of USP7 induces BCR-ABL degradation and chronic myelogenous leukemia cell apoptosis.Cell death & disease · 2021Article
- The Anti-Leukemic Activity of Natural Compounds.Molecules (Basel, Switzerland) · 2021Review
- Gambogic acid: A shining natural compound to nanomedicine for cancer therapeutics.Biochimica et biophysica acta. Reviews on cancer · 2020Review
- Ruscogenin induces ferroptosis in pancreatic cancer cells.Oncology reports · 2020Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeChronic myelogenous leukemia (CML) is characterized by the constitutive activation of Bcr-Abl tyrosine kinase. Bcr-Abl-T315I is the predominant mutation that causes resistance to imatinib, cytotoxic drugs, and the second-generation tyrosine kinase inhibitors. The emergence of imatinib resistance in patients with CML leads to searching for novel approaches to the treatment of CML. Gambogic acid, a small molecule derived from Chinese herb gamboges, has been approved for phase II clinical trial for cancer therapy by the Chinese Food and Drug Administration (FDA). In this study, we investigated the effect of gambogic acid on cell survival or apoptosis in CML cells bearing Bcr-Abl-T315I or wild-type Bcr-Abl. EXPERIMENTAL
designCML cell lines (KBM5, KBM5-T315I, and K562), primary cells from patients with CML with clinical resistance to imatinib, and normal monocytes from healthy volunteers were treated with gambogic acid, imatinib, or their combination, followed by measuring the effects on cell growth, apoptosis, and signal pathways. The in vivo antitumor activity of gambogic acid and its combination with imatinib was also assessed with nude xenografts.
resultsGambogic acid induced apoptosis and cell proliferation inhibition in CML cells and inhibited the growth of imatinib-resistant Bcr-Abl-T315I xenografts in nude mice. Our data suggest that GA-induced proteasome inhibition is required for caspase activation in both imatinib-resistant and -sensitive CML cells, and caspase activation is required for gambogic acid-induced Bcr-Abl downregulation and apoptotic cell death.
conclusionsThese findings suggest an alternative strategy to overcome imatinib resistance by enhancing Bcr-Abl downregulation with the medicinal compound gambogic acid, which may have great clinical significance in imatinib-resistant cancer therapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.