Polyethers isolated from the marine actinobacterium Streptomyces cacaoi inhibit autophagy and induce apoptosis in cancer cells

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dc.contributor.authorKhan, Nasar
dc.contributor.authorYılmaz, Sinem
dc.contributor.authorAksoy, Semiha
dc.contributor.authorUzel, Ataç
dc.contributor.authorTosun, Çiğdem
dc.contributor.authorKırmızıbayrak, Petek Ballar
dc.contributor.authorBedir, Erdal
dc.date.accessioned2021-02-19T21:20:50Z
dc.date.available2021-02-19T21:20:50Z
dc.date.issued2019
dc.departmentALKÜ
dc.description.abstractPolyether compounds, a large group of biologically active metabolites produced by Streptomyces species have been reported to show a variety of bioactivity such as antibacterial, antifungal, antiparasitic, antiviral, and tumour cell cytotoxicity. Since some of these compounds target cancer stem cells and multi-drug resistant cancer cells, this family of compounds have become of high interest. In this study, three polyether-type metabolites (1–3), one of which was a new natural product (3), were isolated from the marine derived Streptomyces cacaoi via antimicrobial activity-guided fractionation studies. As several polyether compounds with structural similarity such as monensin have been linked with autophagy and cell death, we first assessed the cytotoxicity of these three compounds. Compounds 2 and 3, but not 1, were found to be cytotoxic in several cell lines with a higher potency towards cancer cells. Furthermore, 2 and 3 caused accumulation of both autophagy flux markers LC3-II and p62 along with cleavage of caspase-3, caspase-9 and poly (ADP-ribose)polymerase 1 (PARP-1). Interestingly, prolonged treatment of the compounds caused a dramatic downregulation of the proteins related to autophagasome formation in a dose dependent manner. Our findings provide insights on the molecular mechanisms of the polyether-type polyketides, and signify their potency as chemotherapeutic agents through inhibiting autophagy and inducing apoptosis. © 2019 Elsevier B.V.
dc.description.sponsorship2012/BİL/028 109S361
dc.description.sponsorshipThis research was supported by grants from TUBITAK (109S361) and EBILTEM (2012/BİL/028) (E.B.).
dc.identifier.doi10.1016/j.cbi.2019.04.035
dc.identifier.endpage178en_US
dc.identifier.issn0009-2797
dc.identifier.pmid31059704
dc.identifier.scopusqualityQ1
dc.identifier.startpage167en_US
dc.identifier.urihttps://doi.org/10.1016/j.cbi.2019.04.035
dc.identifier.urihttps://hdl.handle.net/20.500.12868/721
dc.identifier.volume307en_US
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthor0-belirlenecek
dc.language.isoen
dc.publisherElsevier Ireland Ltd
dc.relation.ispartofChemico-Biological Interactions
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectApoptosis
dc.subjectAutophagy
dc.subjectMarine actinobacterium polyether antibiotic
dc.titlePolyethers isolated from the marine actinobacterium Streptomyces cacaoi inhibit autophagy and induce apoptosis in cancer cells
dc.typeArticle

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