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dc.creatorDinic, Jelena
dc.creatorNovaković, Miroslav
dc.creatorPodolski-Renic, Ana
dc.creatorStojkovic, Sonja
dc.creatorMandić, Boris
dc.creatorTešević, Vele
dc.creatorVajs, Vlatka
dc.creatorIsakovic, Aleksandra
dc.creatorPesic, Milica
dc.date.accessioned2019-01-30T17:39:36Z
dc.date.available2019-01-30T17:39:36Z
dc.date.issued2014
dc.identifier.issn0032-0943
dc.identifier.urihttp://cer.ihtm.bg.ac.rs/handle/123456789/1434
dc.description.abstractDiarylheptanoids belong to polyphenols, a group of plant secondary metabolites with multiple biological properties. Many of them display antioxidative, cytotoxic, or anticancer actions and are increasingly recognized as potential therapeutic agents. The aim of this study was to evaluate antioxidant and cytoprotective activity of two diarylheptanoids: platyphylloside 5(S)-1,7-di(4-hydroxyphenyl)-3-heptanone-5-O-beta-D-glucopyranoside (1) and its newly discovered analog 5(S)-1,7-di(4-hydroxyphenyl)-5-O-beta-D-[6-(E-p-coumaroylglucopyranosyl)]heptane-3-one (2), both isolated from the bark of black alder (Alnus glutinosa). To that end, we have employed a cancer cell line (NCI-H460), normal human keratinocytes (HaCaT), and peripheral blood mononuclear cells. The effects on cell growth were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Cell death was examined by annexin V/propidium iodide staining on a flow cytometer. Reactive oxygen species production was examined by dihydroethidium staining. Mitochondrial structure and doxorubicin localization were visualized by fluorescent microscopy. Gene expression of manganese superoxide dismutase and hypoxia-inducible factor-1 alpha was determined by reverse transcription polymerase chain reaction. Diarylheptanoids antagonized the effects of either doxorubicin or cisplatin, significantly increasing their IC50 values in normal cells. Diarylheptanoid 1 induced the retention of doxorubicin in cytoplasm and reduced mitochondrial fragmentation associated with doxorubicin application. Diarylheptanoid 2 reduced the reactive oxygen species production induced by cisplatin. Both compounds increased the messenger ribonucleic acid expression of enzymes involved in reactive oxygen species elimination (manganese superoxide dismutase and hypoxia-inducible factor-1 alpha). These results indicate that neutralization of reactive oxygen species is an important mechanism of diarylheptanoid action, although these compounds exert a considerable anticancer effect. Therefore, these compounds may serve as protectors of normal cells during chemotherapy without significantly diminishing the effect of the applied chemotherapeutic.en
dc.publisherGeorg Thieme Verlag Kg, Stuttgart
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41031/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41025/RS//
dc.rightsrestrictedAccess
dc.sourcePlanta Medica
dc.subjectdiarylheptanoiden
dc.subjectAlnus glutinosaen
dc.subjectBetulaceaeen
dc.subjectcurcuminen
dc.subjectdoxorubicinen
dc.subjectcisplatinen
dc.subjectreactive oxygen species (ROS)en
dc.titleAntioxidative Activity of Diarylheptanoids from the Bark of Black Alder (Alnus glutinosa) and Their Interaction with Anticancer Drugsen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractИсаковиц, Aлександра; Стојковиц, Соња; Подолски-Рениц, Aна; Песиц, Милица; Мандиц, Борис; Вајс, Влатка; Новаковић, Мирослав; Тесевиц, Веле; Диниц, Јелена;
dc.citation.volume80
dc.citation.issue13
dc.citation.spage1088
dc.citation.epage1096
dc.citation.other80(13): 1088-1096
dc.citation.rankM21
dc.identifier.pmid25137576
dc.identifier.doi10.1055/s-0034-1382993
dc.identifier.rcubConv_3217
dc.identifier.scopus2-s2.0-84930491748
dc.identifier.wos000341581600005
dc.type.versionpublishedVersion


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