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dc.contributor.authorDahlem, Charlotte
dc.contributor.authorSiow, Wei Xiong
dc.contributor.authorLopatniuk, Maria
dc.contributor.authorTse, William K F
dc.contributor.authorKessler, Sonja M
dc.contributor.authorKirsch, Susanne H
dc.contributor.authorHoppstädter, Jessica
dc.contributor.authorVollmar, Angelika M
dc.contributor.authorMüller, Rolf
dc.contributor.authorLuzhetskyy, Andriy
dc.contributor.authorBartel, Karin
dc.contributor.authorKiemer, Alexandra K
dc.date.accessioned2020-06-17T13:31:30Z
dc.date.available2020-06-17T13:31:30Z
dc.date.issued2020-05-19
dc.identifier.citationCancers (Basel). 2020;12(5):1288. Published 2020 May 19. doi:10.3390/cancers12051288.en_US
dc.identifier.issn2072-6694
dc.identifier.pmid32438733
dc.identifier.doi10.3390/cancers12051288
dc.identifier.urihttp://hdl.handle.net/10033/622302
dc.description.abstractNatural products represent powerful tools searching for novel anticancer drugs. Thioholgamide A (thioA) is a ribosomally synthesized and post-translationally modified peptide, which has been identified as a product of Streptomyces sp. MUSC 136T. In this study, we provide a comprehensive biological profile of thioA, elucidating its effects on different hallmarks of cancer in tumor cells as well as in macrophages as crucial players of the tumor microenvironment. In 2D and 3D in vitro cell culture models thioA showed potent anti-proliferative activities in cancer cells at nanomolar concentrations. Anti-proliferative actions were confirmed in vivo in zebrafish embryos. Cytotoxicity was only induced at several-fold higher concentrations, as assessed by live-cell microscopy and biochemical analyses. ThioA exhibited a potent modulation of cell metabolism by inhibiting oxidative phosphorylation, as determined in a live-cell metabolic assay platform. The metabolic modulation caused a repolarization of in vitro differentiated and polarized tumor-promoting human monocyte-derived macrophages: ThioA-treated macrophages showed an altered morphology and a modulated expression of genes and surface markers. Taken together, the metabolic regulator thioA revealed low activities in non-tumorigenic cells and an interesting anti-cancer profile by orchestrating different hallmarks of cancer, both in tumor cells as well as in macrophages as part of the tumor microenvironment.en_US
dc.language.isoenen_US
dc.publisherMDPIen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectHUVECen_US
dc.subjectM2 macrophagesen_US
dc.subjectOXPHOSen_US
dc.subjectRiPPsen_US
dc.subjectTAM-like macrophagesen_US
dc.subjectflow cytometryen_US
dc.subjectmigrationen_US
dc.subjectmitochondriaen_US
dc.subjectphagocytosisen_US
dc.subjectqPCRen_US
dc.subjectscratch assayen_US
dc.subjectthioviridamide-like compoundsen_US
dc.titleThioholgamide A, a New Anti-Proliferative Anti-Tumor Agent, Modulates Macrophage Polarization and Metabolism.en_US
dc.typeArticleen_US
dc.contributor.departmentHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.en_US
dc.identifier.journalCancersen_US
dc.source.volume12
dc.source.issue5
refterms.dateFOA2020-06-17T13:31:31Z
dc.source.journaltitleCancers
dc.source.countrySwitzerland


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