Bioactivity-guided isolation of cytotoxic secondary metabolites from the roots of Glycyrrhiza glabra and elucidation of their mechanisms of action

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dc.contributor.authorCevik, Dicle
dc.contributor.authorYilmazgoz, S. Burcin
dc.contributor.authorKan, Yuksel
dc.contributor.authorGuzelcan, Ece Akhan
dc.contributor.authorDurmaz, Irem
dc.contributor.authorCetin-Atalay, Rengul
dc.contributor.authorKirmizibekmez, Hasan
dc.date.accessioned2020-03-26T19:52:58Z
dc.date.available2020-03-26T19:52:58Z
dc.date.issued2018
dc.departmentSelçuk Üniversitesien_US
dc.description.abstractLicorice (Glycyrrhiza glabra L.) is one of the most widely used plants worldwide for its various pharmacological activities. The aim of this study was to isolate the potential cytotoxic secondary metabolites from the MeOH extract prepared from the roots of Glycyrrhiza glabra through bioactivity-guided isolation procedure and to elucidate their mechanisms of action. The crude MeOH extract as well as CHCl3 and EtOAc subextracts significantly inhibited cell proliferation on hepatocelullar (Huh7), breast (MCF7) and colorectal (HCT116) cancer cell lines with IC50 values in the range of 5.6 to 33.6 mu g/mL. Chromatographic seperations of the CHCl3 and EtOAc subextracts yielded 13 secondary metabolites. Structures were characterized based on NMR and MS data. Amongst isolates, glabridin (1), 4'-O-methylglabridin (2), beta-amyrin (3), kanzonol U (4), glabrene (7) and tet-rahydroxymethoxychalcone (10) were established to be responsible for in vitro cytotoxicity of G. glabra, exerting the best activity particularly against Huh7 cells. Further mechanistic studies demonstrated that 2 and 7 induced caspase-dependent apoptosis by increasing cytochrome C release and subsequently cleaved caspase-9 level in Huh7 cells. Moreover, both compounds decreased pRb and p21 levels and thus induced the accumulation of Huh-7 cells in subG(1) and G(2)/M phases. Compound 10 which displayed the most potent activity in Hoechst staining and cell cycle assays through G(2)/M arrest, caused cell death by apoptosis in Huh7 cells.en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [115S433]en_US
dc.description.sponsorshipThis study was supported by The Scientific and Technological Research Council of Turkey (TUBITAK, Project No: 115S433).en_US
dc.identifier.doi10.1016/j.indcrop.2018.08.014en_US
dc.identifier.endpage396en_US
dc.identifier.issn0926-6690en_US
dc.identifier.issn1872-633Xen_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage389en_US
dc.identifier.urihttps://dx.doi.org/10.1016/j.indcrop.2018.08.014
dc.identifier.urihttps://hdl.handle.net/20.500.12395/36362
dc.identifier.volume124en_US
dc.identifier.wosWOS:000447569100045en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherELSEVIER SCIENCE BVen_US
dc.relation.ispartofINDUSTRIAL CROPS AND PRODUCTSen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.selcuk20240510_oaigen_US
dc.subjectGlycyrrhiza glabraen_US
dc.subjectSecondary metabolitesen_US
dc.subjectCytotoxic activityen_US
dc.subjectApoptosisen_US
dc.subjectLiver canceren_US
dc.subjectHuh7en_US
dc.titleBioactivity-guided isolation of cytotoxic secondary metabolites from the roots of Glycyrrhiza glabra and elucidation of their mechanisms of actionen_US
dc.typeArticleen_US

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