A promising natural product, pristimerin, results in cytotoxicity against breast cancer stem cells in vitro and xenografts in vivo through apoptosis and an incomplete autopaghy in breast cancer

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dc.authoridDidem Karakaş Zeybek / 0000-0002-3781-6834en_US
dc.authoridEngin Ulukaya / 0000-0003-4875-5472en_US
dc.authoridMerve Erkısa Genel / 0000-0002-3127-742X
dc.authoridPınar Alper / 0000-0001-9631-3551
dc.authorscopusidDidem Karakaş Zeybek / 56422040600
dc.authorscopusidEngin Ulukaya / 6602927353
dc.authorscopusidMerve Erkısa Genel / 57126208900
dc.authorscopusidPınar Alper / 57197858774
dc.authorwosidDidem Karakaş Zeybek / L-6682-2018
dc.authorwosidEngin Ulukaya / K-5792-2018
dc.authorwosidMerve Erkısa Genel / AAM-1001-2020
dc.authorwosidPınar Alper / DUL-1586-2022
dc.contributor.authorCevatemre, Buse
dc.contributor.authorErkısa Genel, Merve
dc.contributor.authorAztopal, Nazlıhan
dc.contributor.authorKarakaş Zeybek, Didem
dc.contributor.authorAlper, Pınar
dc.contributor.authorTsimplouli, Chrisiida
dc.contributor.authorSereti, Evangelia
dc.contributor.authorDimas, Konstantinos
dc.contributor.authorArmutak, Elif I. İkitimur
dc.contributor.authorGürevin, Ebru Gürel
dc.contributor.authorÜvez, Ayça
dc.contributor.authorMori, Mattia
dc.contributor.authorBerardozzi, Simone
dc.contributor.authorIngallina, Cinzia
dc.contributor.authorD'Acquarica, Ilaria
dc.contributor.authorBotta, Bruno
dc.contributor.authorÖzpolat, Bülent
dc.contributor.authorUlukaya, Engin
dc.date.accessioned2020-08-30T20:07:41Z
dc.date.available2020-08-30T20:07:41Z
dc.date.issued2018
dc.departmentİstinye Üniversitesi, Rektörlüken_US
dc.descriptionWOS: 000428102600047en_US
dc.description.abstractSeveral natural products have been suggested as effective agents for the treatment of cancer. Given the important role of CSCs (Cancer Stem Cells) in cancer, which is a trendy hypothesis, it is worth investigating the effects of pristimerin on CSCs as well as on the other malignant cells (MCF-7 and MDA-MB-231) of breast cancer. The anti-growth activity of pristimerin against MCF-7 and MCF-7s (cancer stem cell enriched population) cells was investigated by real time viability monitorization (xCELLigence System (R)) and ATP assay, respectively. Mode of cell death was evaluated using electron and fluorescence microscopies, western blotting (autophagy, apoptosis and ER-stress related markers) and flow cytometry (annexin-V staining, caspase 3/7 activity, BCL-2 and PI3K expressions). Pristimerin showed an anti-growth effect on cancer cells and cancer stem cells with IC50 values ranging at 0.38-1.75 mu M. It inhibited sphere formation at relatively lower doses (<1.56 mu M). Apoptosis was induced in MCF-7 and MCF-7s cells. In addition, extensive cytoplasmic vacuolation was observed, implying an incompleted autophagy as evidenced by the increase of autophagy-related proteins (p62 and LC3-II) with an unfolded protein response (UPR). Pristimerin inhibited the growth of MCF-7 and MDA-MB-231-originated xenografts in NOD.CB17-Prkdc(scid)/J mice. In mice, apoptosis was further confirmed by cleavage of PARP, activation of caspase 3 and/or 7 and TUNEL staining. Taken together, pristimerin shows cytotoxic activity on breast cancer both in vitro and in vivo. It seems to represent a robust promising agent for the treatment of breast cancer. Pristimerin's itself or synthetic novel derivatives should be taken into consideration for novel potent anticancer agent(s). (C) 2017 Elsevier Ltd. All rights reserved.en_US
dc.description.sponsorshipCOST actionEuropean Cooperation in Science and Technology (COST) [1407]en_US
dc.description.sponsorshipThe authors would like to thank Nadine Martinet for collecting and transfering the compound. We appreciate the help of Mehtap KUTLU for preparing the samples for TEM analysis. We would also like to acknowledge Arslan TEKER and Ilknur DAG for their helps with obtaining TEM images at ESOGU ARUM. Lastly, we are proud to mention the COST action 1407 for its support.en_US
dc.identifier.citationCevatemre, B., Erkısa, M., Aztopal, N., Karakas, D., Alper, P., Tsimplouli, C., … Ulukaya, E. (2018). A promising natural product, pristimerin, results in cytotoxicity against breast cancer stem cells in vitro and xenografts in vivo through apoptosis and an incomplete autopaghy in breast cancer. Pharmacological Research, 129, 500–514. https://doi.org/10.1016/j.phrs.2017.11.027en_US
dc.identifier.doi10.1016/j.phrs.2017.11.027en_US
dc.identifier.endpage514en_US
dc.identifier.issn1043-6618en_US
dc.identifier.pmid29197639en_US
dc.identifier.scopus2-s2.0-85035362601en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage500en_US
dc.identifier.urihttps://doi.org/10.1016/j.phrs.2017.11.027
dc.identifier.urihttps://hdl.handle.net/20.500.12713/813
dc.identifier.volume129en_US
dc.identifier.wosWOS:000428102600047en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorErkısa Genel, Merveen_US
dc.institutionauthorKarakaş Zeybek, Didemen_US
dc.institutionauthorAlper, Pınaren_US
dc.institutionauthorUlukaya, Enginen_US
dc.language.isoenen_US
dc.publisherAcademic Press Ltd- Elsevier Science Ltden_US
dc.relation.ispartofPharmacological Researchen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectTriterpenoiden_US
dc.subjectMammosphereen_US
dc.subjectEndoplasmic Reticulum Stressen_US
dc.subjectCytoplasmic Vacuolationen_US
dc.titleA promising natural product, pristimerin, results in cytotoxicity against breast cancer stem cells in vitro and xenografts in vivo through apoptosis and an incomplete autopaghy in breast canceren_US
dc.typeArticleen_US

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