ArticleMolecular & cellular proteomics : MCP2016
Proteomic Analysis Revealed the Important Role of Vimentin in Human Cervical Carcinoma HeLa Cells Treated With Gambogic Acid.
Article in Molecular & cellular proteomics : MCP, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 37 citations in OpenAlex.
- Antitumor effects and mechanisms of traditional Chinese medicine gamboge: A review.Frontiers in pharmacology · 2025Review
- 5-Fluorouracil dose escalation generated desensitized colorectal cancer cells with reduced expression of protein methyltransferases and no epithelial-to-mesenchymal transition potential.Oncology research · 2024Article
- Review
- Unveiling diagnostic and therapeutic strategies for cervical cancer: biomarker discovery through proteomics approaches and exploring the role of cervical cancer stem cells.Frontiers in oncology · 2023Review
- Research Progress in the Field of Gambogic Acid and Its Derivatives as Antineoplastic Drugs.Molecules (Basel, Switzerland) · 2022Review
- Unravelling Novel Roles of Salivary Exosomes in the Regulation of Human Corneal Stromal Cell Migration and Wound Healing.International journal of molecular sciences · 2022Article
- Vimentin Tail Segments Are Differentially Exposed at Distinct Cellular Locations and in Response to Stress.Frontiers in cell and developmental biology · 2022Article
- An update of label-free protein target identification methods for natural active products.Theranostics · 2022Review
- Target identification of anticancer natural products using a chemical proteomics approach.RSC advances · 2021Review
- Network Pharmacology Analysis and Experimental Pharmacology Study Explore the Mechanism of Gambogic Acid against Endometrial Cancer.ACS omega · 2021Article
- Currently Available Strategies for Target Identification of Bioactive Natural Products.Frontiers in chemistry · 2021Review
- Gambogic acid: A shining natural compound to nanomedicine for cancer therapeutics.Biochimica et biophysica acta. Reviews on cancer · 2020Review
- Vimentin as a Multifaceted Player and Potential Therapeutic Target in Viral Infections.International journal of molecular sciences · 2020Review
- Reversal of Epithelial-Mesenchymal Transition by Natural Anti-Inflammatory and Pro-Resolving Lipids.Cancers · 2019Review
- Discovery of the Consistently Well-Performed Analysis Chain for SWATH-MS Based Pharmacoproteomic Quantification.Frontiers in pharmacology · 2018Article
- USP14 de-ubiquitinates vimentin and miR-320a modulates USP14 and vimentin to contribute to malignancy in gastric cancer cells.Oncotarget · 2017Article
- Gambogic acid identifies an isoform-specific druggable pocket in the middle domain of Hsp90β.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gambogic acid (GA) is an anticancer agent in phase IIb clinical trial in China. In HeLa cells, GA inhibited cell proliferation, induced cell cycle arrest at G2/M phase and apoptosis, as showed by results of MTT assay and flow cytometric analysis. Possible target-related proteins of GA were searched using comparative proteomic analysis (2-DE) and nine proteins at early (3 h) stage together with nine proteins at late (24 h) stage were found. Vimentin was the only target-related protein found at both early and late stage. Results of both 2-DE analysis and Western blotting assay suggested cleavage of vimentin induced by GA. MS/MS analysis of cleaved vimentin peptides indicated possible cleavage sites of vimentin at or near ser51 and glu425. Results of targeted proteomic analysis showed that GA induced change in phosphorylation state of the vimentin head domain (aa51-64). Caspase inhibitors could not abrogate GA-induced cleavage of vimentin. Over-expression of vimentin ameliorated cytotoxicity of GA in HeLa cells. The GA-activated signal transduction, from p38 MAPK, heat shock protein 27 (HSP27), vimentin, dysfunction of cytoskeleton, to cell death, was predicted and then confirmed. Results of animal study showed that GA treatment inhibited tumor growth in HeLa tumor-bearing mice and cleavage of vimentin could be observed in tumor xenografts of GA-treated animals. Results of immunohistochemical staining also showed down-regulated vimentin level in tumor xenografts of GA-treated animals. Furthermore, compared with cytotoxicity of GA in HeLa cells, cytotoxicity of GA in MCF-7 cells with low level of vimentin was weaker whereas cytotoxicity of GA in MG-63 cells with high level of vimentin was stronger. These results indicated the important role of vimentin in the cytotoxicity of GA. The effects of GA on vimentin and other epithelial-to-mesenchymal transition (EMT) markers provided suggestion for better usage of GA in clinic.
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