ArticleCell death & disease2019
Gambogic acid triggers vacuolization-associated cell death in cancer cells via disruption of thiol proteostasis.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41 citing papers in PubMed, 78 citations in OpenAlex.
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- Osimertinib activates TFEB to trigger hepatocyte cytoplasmic vacuolation-associated cell death.Cell communication and signaling : CCS · 2026Article
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- Potent Inducers of Paraptosis through Electronic Tuning of Hemicyanine Electrophiles.Journal of the American Chemical Society · 2025Article
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- Gilteritinib suppresses prostate cancer cell proliferation and migration and induces ER stress-mediated non-autophagic cytoplasmic vacuolization cell death.Medical oncology (Northwood, London, England) · 2025Article
- Graphene Nanocomposites in the Targeting Tumor Microenvironment: Recent Advances in TME Reprogramming.International journal of molecular sciences · 2025Review
- Antitumor effects and mechanisms of traditional Chinese medicine gamboge: A review.Frontiers in pharmacology · 2025Review
- Exploring paraptosis as a therapeutic approach in cancer treatment.Journal of biomedical science · 2024Review
- Norcantharidin inhibits the malignant progression of cervical cancer by inducing endoplasmic reticulum stress.Molecular medicine reports · 2024Article
- Targeting paraptosis in cancer: opportunities and challenges.Cancer gene therapy · 2024Review
- Paraptosis: a non-classical paradigm of cell death for cancer therapy.Acta pharmacologica Sinica · 2024Review
- Akt enhances the vulnerability of cancer cells to VCP/p97 inhibition-mediated paraptosis.Cell death & disease · 2024Article
- Graphene-Based Photodynamic Therapy and Overcoming Cancer Resistance Mechanisms: A Comprehensive Review.International journal of nanomedicine · 2024Review
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- Enniatin A inhibits the chaperone Hsp90 and unleashes the immune system against triple-negative breast cancer.iScience · 2023Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gambogic acid (GA), a xanthonoid extracted from the resin of the tree, Garcinia hanburyi, was recently shown to exert anticancer activity in multiple studies, but the underlying action mechanism remains unclear. Here, we show that GA induces cancer cell death accompanied by vacuolation in vitro and in vivo. This GA-induced vacuolation in various cancer cells was derived from dilation of the endoplasmic reticulum (ER) and mitochondria, and was blocked by cycloheximide. These findings suggest that GA kills cancer cells by inducing paraptosis, a vacuolization-associated cell death. We found that megamitochondria formation, which arose from the fusion of swollen mitochondria, preceded the fusion of ER-derived vacuoles. GA-induced proteasomal inhibition was found to contribute to the ER dilation and ER stress seen in treated cancer cells, and megamitochondria formation was followed by mitochondrial membrane depolarization. Interestingly, GA-induced paraptosis was effectively blocked by various thiol-containing antioxidants, and this effect was independent of ROS generation. We observed that GA can react with cysteinyl thiol to form Michael adducts, suggesting that the ability of GA to covalently modify the nucleophilic cysteinyl groups of proteins may cause protein misfolding and subsequent accumulation of misfolded proteins within the ER and mitochondria. Collectively, our findings show that disruption of thiol proteostasis and subsequent paraptosis may critically contribute to the anti-cancer effects of GA.
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