ArticleMolecular cancer therapeutics2008
Gambogic acid is an antagonist of antiapoptotic Bcl-2 family proteins.
Article in Molecular cancer therapeutics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 82 citations in OpenAlex.
- Beyond cytotoxicity: molecular mechanisms of natural products as multi-targeting modulators and chemo-sensitizers in oncology.Frontiers in pharmacology · 2026Review
- Gambogic acid suppresses osteosarcoma progression through upregulation of FOXO3a.Discover oncology · 2025Article
- Antitumor effects and mechanisms of traditional Chinese medicine gamboge: A review.Frontiers in pharmacology · 2025Review
- Inhibition of SRC-3 as a potential therapeutic strategy for aggressive mantle cell lymphoma.PloS one · 2024Article
- Modulating the p53-MDM2 pathway: the therapeutic potential of natural compounds in cancer treatment.EXCLI journal · 2024Review
- Garcinolic Acid Distinguishes Between GACKIX Domains and Modulates Interaction Networks.Chembiochem : a European journal of chemical biology · 2023Article
- Bcl-B: an "unknown" protein of the Bcl-2 family.Biology direct · 2023Review
- Mechanism of anticancer effect of gambogic acid on gastric signet ring cell carcinoma.Medical oncology (Northwood, London, England) · 2023Article
- The multi-kinase inhibitor TG02 induces apoptosis and blocks B-cell receptor signaling in chronic lymphocytic leukemia through dual mechanisms of action.Blood cancer journal · 2021Article
- Pharmacological targeting of MCL-1 promotes mitophagy and improves disease pathologies in an Alzheimer's disease mouse model.Nature communications · 2020Article
- Gambogic Acid as a Candidate for Cancer Therapy: A Review.International journal of nanomedicine · 2020Review
- MCL-1 inhibition in cancer treatment.OncoTargets and therapy · 2018Review
- Inhibition of inwardly rectifying Kir2.x channels by the novel anti-cancer agent gambogic acid depends on both pore block and PIPNaunyn-Schmiedeberg's archives of pharmacology · 2017Article
- Article
- Novel Natural Product-like Caged Xanthones Bearing a Carbamate Moiety Exhibit Antitumor Potency and Anti-Angiogenesis Activity In vivo.Scientific reports · 2016Article
- Tumor neovasculature-targeted cationic PEGylated liposomes of gambogic acid for the treatment of triple-negative breast cancer.Drug delivery · 2016Article
- Anti-leukemic, anti-lung, and anti-breast cancer potential of the microbial polyketide 2, 4-diacetylphloroglucinol (DAPG) and its interaction with the metastatic proteins than the antiapoptotic Bcl-2 proteins.Molecular and cellular biochemistry · 2016Article
- Recent research on bioactive xanthones from natural medicine: Garcinia hanburyi.AAPS PharmSciTech · 2015Review
- Gambogic acid induces apoptosis in diffuse large B-cell lymphoma cells via inducing proteasome inhibition.Scientific reports · 2015Article
- Methyl jasmonate sensitizes human bladder cancer cells to gambogic acid-induced apoptosis through down-regulation of EZH2 expression by miR-101.British journal of pharmacology · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The natural product gambogic acid (GA) has been reported to have cytotoxic activity against tumor cells in culture and was identified as an active compound in a cell-based high-throughput screening assay for activators of caspases, proteases involved in apoptosis. Using the antiapoptotic Bcl-2 family protein, Bfl-1, as a target for screening of a library of natural products, we identified GA as a competitive inhibitor that displaced BH3 peptides from Bfl-1 in a fluorescence polarization assay. Analysis of competition for BH3 peptide binding revealed that GA inhibits all six human Bcl-2 family proteins to various extents, with Mcl-1 and Bcl-B the most potently inhibited [concentrations required for 50% inhibition (IC(50)), < 1 micromol/L]. Competition for BH3 peptide binding was also confirmed using a time-resolved fluorescence resonance energy transfer assay. GA functionally inhibited the antiapoptotic Bcl-2 family proteins as shown by experiments using isolated mitochondria in which recombinant purified Bcl-2 family proteins suppress SMAC release in vitro, showing that GA neutralizes their suppressive effects on mitochondria in a concentration-dependent manner. GA killed tumor cell lines via an apoptotic mechanism, whereas analogues of GA with greatly reduced potency at BH3 peptide displacement showed little or no cytotoxic activity. However, GA retained cytotoxic activity against bax-/-bak-/- cells in which antiapoptotic Bcl-2 family proteins lack a cytoprotective phenotype, implying that GA also has additional targets that contribute to its cytotoxic mechanism. Altogether, the findings suggest that suppression of antiapoptotic Bcl-2 family proteins may be among the cytotoxic mechanisms by which GA kills tumor cells.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.