Mechanisms of action of cytotoxic phenolic compounds from Glycyrrhiza iconica roots

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dc.contributor.authorCevik, Dicle
dc.contributor.authorKan, Yuksel
dc.contributor.authorKirmizibekmez, Hasan
dc.date.accessioned2020-03-26T20:15:09Z
dc.date.available2020-03-26T20:15:09Z
dc.date.issued2019
dc.departmentSelçuk Üniversitesi, Ziraat Fakültesi, Tarla Bitkileri Bölümüen_US
dc.description.abstractBackground: Glycyrrhiza (licorice) species are rich in bioactive secondary metabolites and their roots are used traditionally for the treatment of several diseases. In recent years, secondary metabolites of licorice are gaining popularity, especially due to their significant cytotoxic and antitumor effects. However, Glycyrrhiza iconica, an endemic species to Turkey, was not investigated in terms of its anticancer secondary metabolites previously. Purpose: This study aimed to isolate the cytotoxic compounds from G. iconica through bioactivity-guided fractionation and to elucidate mechanisms of action of the most potent compounds. Methods: Total MeOH extract and CHCl3, EtOAc, n-buOH and rH(2)O subextracts were prepared from G. iconica roots. Sequential chromatographic techniques were conducted for the isolation studies. The chemical structures of the isolates were established based on NMR and HR-MS analysis. Sulforhodamine B assay was used to evaluate the cytotoxic activity of extracts, main fractions as well as isolates against hepatocellular (Huh7), breast (MCF7) and colorectal (HCT116) cancer cell lines. The mechanisms underlying the cytotoxicity of the most active compounds in Huh7 cells were elucidated by using Hoechst staining, Fluorescence-activated cell sorting and Western blot assays. Results: A new dihydrochalcone, iconichalcone (1) along with 15 known phenolic compounds were isolated from the active CHCl3, EtOAc and n-buOH subextracts. Compounds 2-5, 7-16 were found to be responsible for the in vitro cytotoxic activity of G. iconica against all tested cancer cell lines with IC50 values ranging from 2.4 to 33 mu M. Amongst these compounds, licoricidin (10), dehydroglyasperin C (12), iconisoflaven (13) and 1-methoxyficifolinol (15) were found to be the most active compounds according to SRB and real time bioactivity assays and submitted to further mechanistic investigations in Huh7 cells. Compounds 10, 12, 13 and 15 caused accumulation of cells in different phases of cell cycle. Moreover, 10, 12, 13 and 15 induced apoptosis through caspase activation. Besides, 12 showed activation of p53 expression and thus G(2)/M arrest as well as a condensed nuclei, established very promising results. Conclusion: The results demonstrated that the aforementioned compounds, particularly 12 could be potential lead molecules for anticancer drug development that deserve further in vivo and clinical investigations.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 financially supported by The Scientific and Technological Research Council of Turkey (TUBITAK, Project No: 115S433). The authors thank Dr. Ece Akhan Guzelcan and Prof. Dr. Rengul Cetin Atalay (Cancer Systems Biology Laboratory, Graduate School of Informatics, METU, TR-06800, Ankara, Turkey) for performing bioactivity assays.en_US
dc.identifier.citationÇevik, D., Kan, Y., Kırmızıbekmez, H. (2019). Mechanisms Of Action Of Cytotoxic Phenolic Compounds From Glycyrrhiza İconica Roots. Phytomedicine, 58, 152872.
dc.identifier.doi10.1016/j.phymed.2019.152872en_US
dc.identifier.issn0944-7113en_US
dc.identifier.issn1618-095Xen_US
dc.identifier.pmid30826527en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://dx.doi.org/10.1016/j.phymed.2019.152872
dc.identifier.urihttps://hdl.handle.net/20.500.12395/37992
dc.identifier.volume58en_US
dc.identifier.wosWOS:000473047100030en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorKan, Yuksel
dc.language.isoenen_US
dc.publisherELSEVIER GMBHen_US
dc.relation.ispartofPHYTOMEDICINEen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.selcuk20240510_oaigen_US
dc.subjectGlycyrrhiza iconicaen_US
dc.subjectSecondary metabolitesen_US
dc.subjectCytotoxic activityen_US
dc.subjectApoptosisen_US
dc.subjectLiver canceren_US
dc.subjectHuh7en_US
dc.titleMechanisms of action of cytotoxic phenolic compounds from Glycyrrhiza iconica rootsen_US
dc.typeArticleen_US

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