{"data":{"id":"10.6084/m9.figshare.c.2122238.v1","type":"dois","attributes":{"doi":"10.6084/m9.figshare.c.2122238.v1","prefix":"10.6084","suffix":"m9.figshare.c.2122238.v1","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Zhao, Xuejiao","givenName":"Xuejiao","familyName":"Zhao","affiliation":[],"nameIdentifiers":[]},{"name":"Fang, Yong","givenName":"Yong","familyName":"Fang","affiliation":[],"nameIdentifiers":[]},{"name":"Yang, Yang","givenName":"Yang","familyName":"Yang","affiliation":[],"nameIdentifiers":[]},{"name":"Qin, Yu","givenName":"Yu","familyName":"Qin","affiliation":[],"nameIdentifiers":[]},{"name":"Wu, Peng","givenName":"Peng","familyName":"Wu","affiliation":[],"nameIdentifiers":[]},{"name":"Wang, Ting","givenName":"Ting","familyName":"Wang","affiliation":[],"nameIdentifiers":[]},{"name":"Lai, Huiling","givenName":"Huiling","familyName":"Lai","affiliation":[],"nameIdentifiers":[]},{"name":"Meng, Li","givenName":"Li","familyName":"Meng","affiliation":[],"nameIdentifiers":[]},{"name":"Wang, Daowen","givenName":"Daowen","familyName":"Wang","affiliation":[],"nameIdentifiers":[]},{"name":"Zheng, Zhihui","givenName":"Zhihui","familyName":"Zheng","affiliation":[],"nameIdentifiers":[]},{"name":"Lu, Xinhua","givenName":"Xinhua","familyName":"Lu","affiliation":[],"nameIdentifiers":[]},{"name":"Zhang, Hua","givenName":"Hua","familyName":"Zhang","affiliation":[],"nameIdentifiers":[]},{"name":"Gao, Qinglei","givenName":"Qinglei","familyName":"Gao","affiliation":[],"nameIdentifiers":[]},{"name":"Zhou, Jianfeng","givenName":"Jianfeng","familyName":"Zhou","affiliation":[],"nameIdentifiers":[]},{"name":"Ma, Ding","givenName":"Ding","familyName":"Ma","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"Elaiophylin, a novel autophagy inhibitor, exerts antitumor activity as a single agent in ovarian cancer cells"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2015,"subjects":[{"subject":"Biochemistry"},{"subject":"Cell Biology"},{"subject":"Molecular Biology"},{"subject":"Pharmacology"},{"subject":"Chemical Sciences not elsewhere classified"},{"subject":"Immunology"},{"subject":"FOS: Clinical medicine","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Biological Sciences not elsewhere classified"},{"subject":"Cancer"},{"subject":"Hematology"},{"subject":"Virology"}],"contributors":[],"dates":[{"date":"2015-12-05","dateType":"Created"},{"date":"2019-08-19","dateType":"Updated"},{"date":"2015","dateType":"Issued"}],"language":null,"types":{"ris":"GEN","bibtex":"misc","citeproc":"article","schemaOrg":"Collection","resourceType":"Collection","resourceTypeGeneral":"Collection"},"relatedIdentifiers":[{"relationType":"IsIdenticalTo","relatedIdentifier":"10.6084/m9.figshare.c.2122238","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":[],"formats":[],"version":null,"rightsList":[{"rights":"Creative Commons Attribution 4.0 International","rightsUri":"https://creativecommons.org/licenses/by/4.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc-by-4.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"Currently, targeting the autophagic pathway is regarded as a promising new strategy for cancer drug discovery. Here, we screened the North China Pharmaceutical Group Corporation's pure compound library of microbial origin using GFP-LC3B-SKOV3 cells and identified elaiophylin as a novel autophagy inhibitor. Elaiophylin promotes autophagosome accumulation but blocks autophagic flux by attenuating lysosomal cathepsin activity, resulting in the accumulation of SQSTM1/p62 in various cell lines. Moreover, elaiophylin destabilizes lysosomes as indicated by LysoTracker Red staining and CTSB/cathepsin B and CTSD/ cathepsin D release from lysosomes into the cytoplasm. Elaiophylin eventually decreases cell viability, especially in combination with cisplatin or under hypoxic conditions. Furthermore, administration of a lower dose (2 mg/kg) of elaiophylin as a single agent achieves a significant antitumor effect without toxicity in an orthotopic ovarian cancer model with metastasis; however, high doses (8 mg/kg) of elaiophylin lead to dysfunction of Paneth cells, which resembles the intestinal phenotype of ATG16L1-deficient mice. Together, these results provide a safe therapeutic window for potential clinical applications of this compound. Our results demonstrate, for the first time, that elaiophylin is a novel autophagy inhibitor, with significant antitumor efficacy as a single agent or in combination in human ovarian cancer cells, establishing the potential treatment of ovarian cancer by this compound.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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