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dc.contributor.authorNeophytou, Christiana M.en
dc.contributor.authorConstantinou, Constantinaen
dc.contributor.authorPapageorgis, P.en
dc.contributor.authorConstantinou, Andreas I.en
dc.creatorNeophytou, Christiana M.en
dc.creatorConstantinou, Constantinaen
dc.creatorPapageorgis, P.en
dc.creatorConstantinou, Andreas I.en
dc.description.abstractd-alpha-tocopheryl polyethylene glycol succinate (TPGS) is a vitamin E derivative that has been intensively applied as a vehicle for drug delivery systems to enhance drug solubility and increase the oral bioavailability of anti-cancer drugs. Recently, it has been reported that TPGS acts as an anti-cancer agent alone or synergistically with chemotherapeutic drugs and increases the efficacy of nanoparticle formulations. In this study, we investigated the antitumor efficacy and the molecular mechanism of action of TPGS in breast cancer cell lines. Our results show that TPGS can induce G1/S cell cycle arrest and apoptosis in breast cancer cell lines (MCF-7 and MDA-MB-231) but not in "normal" (non-tumorigenic) immortalized cells (MCF-10A and MCF-12F). An investigation of the molecular mechanism of action of TPGS reveals that induction of G1/S phase cell cycle arrest is associated with upregulation of P21 and P27Kip1 proteins. Induction of apoptosis by TPGS involves the inhibition of phospho-AKT and the downregulation of the anti-apoptotic proteins Survivin and Bcl-2. Interestingly, our results also suggest that TPGS induces both caspase -dependent and -independent apoptotic signaling pathways and that this vitamin E derivative is selectively cytotoxic in breast cancer cell lines. When compared to the Survivin inhibitor YM155, TPGS was shown to be more selective for cancer cell growth inhibition. Overall our results suggest that TPGS may not only be useful as a carrier molecule for drug delivery, but may also exert intrinsic therapeutic effects suggesting that it may promote a synergistic interaction with formulated chemotherapeutic drugs. © 2014 Elsevier Inc.en
dc.sourceBiochemical pharmacologyen
dc.subjectBreast Neoplasmsen
dc.subjectcontrolled studyen
dc.subjectcancer growthen
dc.subjectpriority journalen
dc.subjectdrug efficacyen
dc.subjectantineoplastic activityen
dc.subjectprotein bcl 2en
dc.subjectCell cycleen
dc.subjectunclassified drugen
dc.subjectBreast canceren
dc.subjectdown regulationen
dc.subjectsignal transductionen
dc.subjectdrug mechanismen
dc.subjectdrug potentiationen
dc.subjectdrug selectivityen
dc.subjectPolyethylene Glycolsen
dc.subjectcancer cellen
dc.subjecthuman cellen
dc.subjectcell deathen
dc.subjectBase Sequenceen
dc.subjectDNA Primersen
dc.subjectgene overexpressionen
dc.subjectcyclin dependent kinase inhibitor 1Ben
dc.subjectprotein kinase Ben
dc.subjectprotein p21en
dc.subjectgene silencingen
dc.subjectdrug cytotoxicityen
dc.subjectenzyme phosphorylationen
dc.subjectcancer cell cultureen
dc.subjectdrug delivery systemen
dc.subjectEnzyme-Linked Immunosorbent Assayen
dc.subjectenzyme inhibitionen
dc.subjectcancer inhibitionen
dc.subjectconcentration responseen
dc.subjectdrug carrieren
dc.subjectWestern blottingen
dc.subjectcell cycle arresten
dc.subjectG1 phase cell cycle checkpointen
dc.subjectS phase cell cycle checkpointen
dc.subjectCell Line, Tumoren
dc.subjectBlotting, Westernen
dc.subjectVitamin Een
dc.subjectalpha tocopherol succinateen
dc.subjectReal-Time Polymerase Chain Reactionen
dc.subjectAKT pathwayen
dc.subjectbreast cellen
dc.subjectdelta alpha tocopheryl polyethylene glycol succinateen
dc.subjectInhibitor of Apoptosis Proteinsen
dc.subjectmcf 10a cellen
dc.subjectmcf 12f cellen
dc.subjectsepantronium bromideen
dc.titleD-alpha-tocopheryl polyethylene glycol succinate (TPGS) induces cell cycle arrest and apoptosis selectively in Survivin-overexpressing breast cancer cellsen
dc.description.endingpage42Σχολή Θετικών και Εφαρμοσμένων Επιστημών / Faculty of Pure and Applied SciencesΤμήμα Βιολογικών Επιστημών / Department of Biological Sciences
dc.description.notes<p>Tradenames: ym 155, Selleck, United Statesen
dc.description.notesManufacturers: Eastman Kodak, United Statesen
dc.description.notesSelleck, United Statesen
dc.description.notesCited By :38</p>en
dc.contributor.orcidConstantinou, Andreas I. [0000-0003-0365-1821]

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