{"doi":"10.3892/ijo.2015.3249","title":"Gambogic acid induces apoptosis and sensitizes TRAIL-mediated apoptosis through downregulation of cFLIPL in renal carcinoma Caki cells","abstract":null,"journal":"International Journal of Oncology","year":2016,"id":682438,"datarank":0.4566783656585135,"base_score":3.044522437723423,"endowment":3.044522437723423,"self_citation_contribution":0.4566783656585135,"citation_network_contribution":0.0,"self_endowment_contribution":0.4566783656585135,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1782878,"name":"JOO-YOUNG KIM","orcid":null,"position":1,"is_corresponding":false},{"id":1782879,"name":"EON-GI SUNG","orcid":null,"position":2,"is_corresponding":false},{"id":1782880,"name":"EUN-AE KIM","orcid":null,"position":3,"is_corresponding":false},{"id":1782881,"name":"TAE-JIN LEE","orcid":null,"position":4,"is_corresponding":false},{"id":1782877,"name":"JI HOON JANG","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Gambogic acid induces apoptosis and sensitizes TRAIL-mediated apoptosis through downregulation of cFLIPL in renal carcinoma Caki cells","abstract":"Gambogic acid (GA) is a natural compound derived from brownish gamboge resin that shows a range of bioactivity, such as antitumor and antimicrobial properties. Although, GA is already known to induce cell death in a variety of cancer cells, the molecular basis for GA-induced cell death in renal cancer cells is unclear. In this study, a treatment with GA induced cell death in human renal carcinoma Caki cells in a dose-dependent manner. Treatment of Caki cells with GA decreased the levels of antiapoptotic proteins, such as Bcl-2 and XIAP in a dose-dependent manner. In addition, GA decreased the expression of the cFLIPL protein, which was downregulated at the transcriptional level without any change in the levels of cFLIPs expression. z-VAD (pan-caspase inhibitor) partially blocked GA-mediated cell death. GA-induced apoptotic cell death in Caki cells is mediated partly by the AIF translocation from the mitochondria into the nucleus via a caspase-independent pathway. In contrast, N-acetylcysteine (NAC), a ROS scavenger, had no effect on GA-induced cell death. The restoration of cFLIPL attenuated GA-induced cell death in Caki cells. Furthermore, a sub-toxic dose of GA sensitized TRAIL-mediated apoptosis in Caki cells. Pretreatment with z-VAD completely blocked GA plus TRAIL-mediated apoptosis. On the contrary, pretreatment with NAC partially inhibited GA plus TRAIL-induced apoptosis. Our findings suggested that GA induces apoptosis via the downregulation of cFLIPL and sensitized TRAIL-mediated apoptosis in Caki cells.","is_dataset_classified":null,"base_score":3.044522437723423,"endowment":3.044522437723423,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26648023","pmcid":null,"openalex_id":"https://openalex.org/W2178462734","authors":[],"funders":[],"total_grants":0,"fwci":2.9965,"citation_percentile":0.9117629,"influential_citations":0,"citation_trend":[{"year":2016,"count":1},{"year":2017,"count":5},{"year":2019,"count":3},{"year":2020,"count":1},{"year":2021,"count":2},{"year":2022,"count":3},{"year":2023,"count":2},{"year":2024,"count":2},{"year":2025,"count":1}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"http://www.spandidos-publications.com/10.3892/ijo.2015.3249/download","host_type":"journal"},{"url":"http://www.spandidos-publications.com/10.3892/ijo.2015.3249/download","host_type":"publisher"},{"url":"https://spandidos-publications.com/10.3892/ijo.2015.3249/download","host_type":"publisher"},{"url":"https://doi.org/10.3892/ijo.2015.3249","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26648023","host_type":"repository"}],"fields_of_study":["Natural Compound Pharmacology Studies","Synthesis of Organic Compounds","Cancer-related Molecular Pathways"],"mesh_terms":["Acetylcysteine","Carcinoma, Renal Cell","Humans","Gene Expression Regulation, Neoplastic","Apoptosis","Reactive Oxygen Species","Xanthones","Cell Line, Tumor","Cell Proliferation","TNF-Related Apoptosis-Inducing Ligand","CASP8 and FADD-Like Apoptosis Regulating Protein"],"keywords":["Gambogic acid","Apoptosis","Programmed cell death","XIAP","Downregulation and upregulation","Cancer cell","Cell biology","Cell","Staurosporine","Cancer research","Caspase","Biology","Chemistry","Signal transduction","Cancer","Biochemistry","Protein kinase C"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T20:22:42.230773Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}