Anticancer and Multidrug Resistance-Reversal Effects of Solanidine Analogs Synthetized from Pregnadienolone Acetate

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dc.contributor.authorZupko, Istvan
dc.contributor.authorMolnar, Judit
dc.contributor.authorRethy, Borbala
dc.contributor.authorMinorics, Renata
dc.contributor.authorFrank, Eva
dc.contributor.authorWoelfling, Janos
dc.contributor.authorMolnar, Joseph
dc.contributor.authorOcsovszki, Imre
dc.contributor.authorTopcu, Zeki
dc.contributor.authorBito, Tamas
dc.contributor.authorPuskas, Laszlo G.
dc.date.accessioned2019-10-27T22:05:24Z
dc.date.available2019-10-27T22:05:24Z
dc.date.issued2014
dc.departmentEge Üniversitesien_US
dc.description.abstractA set of solanidine analogs with antiproliferative properties were recently synthetized from pregnadienolone acetate, which occurs in Nature. The aim of the present study was an in vitro characterization of their antiproliferative action and an investigation of their multidrug resistance-reversal activity on cancer cells. Six of the compounds elicited the accumulation of a hypodiploid population of HeLa cells, indicating their apoptosis-inducing character, and another one caused cell cycle arrest at the G2/M phase. The most effective agents inhibited the activity of topoisomerase I, as evidenced by plasmid supercoil relaxation assays. One of the most potent analogs down-regulated the expression of cell-cycle related genes at the mRNA level, including tumor necrosis factor alpha and S-phase kinase-associated protein 2, and induced growth arrest and DNA damage protein 45 alpha. Some of the investigated compounds inhibited the ABCB1 transporter and caused rhodamine-123 accumulation in murine lymphoma cells transfected by human MDR1 gene, expressing the efflux pump (L5178). One of the most active agents in this aspect potentiated the antiproliferative action of doxorubicin without substantial intrinsic cytostatic capacity. The current results indicate that the modified solanidine skeleton is a suitable substrate for the rational design and synthesis of further innovative drug candidates with anticancer activities.en_US
dc.description.sponsorshipHungarian Scientific Research FundOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [OTKA K-109293]; European UnionEuropean Union (EU); European Social FundEuropean Social Fund (ESF) [TAMOP-4.2.2.A-11/1/KONV-2012-0035]en_US
dc.description.sponsorshipFinancial support from the Hungarian Scientific Research Fund (OTKA K-109293) is gratefully acknowledged. This study was financially supported by the European Union and co-financed by the European Social Fund; project number: TAMOP-4.2.2.A-11/1/KONV-2012-0035.en_US
dc.identifier.doi10.3390/molecules19022061en_US
dc.identifier.endpage2076en_US
dc.identifier.issn1420-3049
dc.identifier.issue2en_US
dc.identifier.pmid24549231en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage2061en_US
dc.identifier.urihttps://doi.org/10.3390/molecules19022061
dc.identifier.urihttps://hdl.handle.net/11454/48412
dc.identifier.volume19en_US
dc.identifier.wosWOS:000334418200043en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherMdpien_US
dc.relation.ispartofMoleculesen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectsolanidine analogen_US
dc.subjectanticancer actionen_US
dc.subjectefflux pumpen_US
dc.titleAnticancer and Multidrug Resistance-Reversal Effects of Solanidine Analogs Synthetized from Pregnadienolone Acetateen_US
dc.typeArticleen_US

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