Tsimplouli, ChrisiidaSereti, EvangeliaDimas, KonstantinosIlkay Armutak, ElifGurevin, Ebru GurelÜvez, AyçaMori, MattiaBerardozzi, SimoneIngallina, CinziaD'Acquarica, IlariaBotta, BrunoÖzpolat, BülentUlukaya, Engin2022-12-212022-12-212017-12-02Cevatemre, B. vd. (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, 500-514.1043-6618https://doi.org/10.1016/j.phrs.2017.11.027https://www.sciencedirect.com/science/article/pii/S1043661817309933http://hdl.handle.net/11452/29994Several 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).eninfo:eu-repo/semantics/closedAccessTriterpenoidMammosphereEndoplasmic reticulum stressCytoplasmic vacuolationSignaling pathwayAutophagyDegradationCarcinomaProliferationPalladium(ıı)DoxorubicinTriterpenesMetastasisAnimalsAntineoplastic agentsApoptosisAutophagyBiological productsCell line, tumorHumansMammary neoplasms, experimentalMiceNeoplastic stem cellsTriterpenesXenograft model antitumor assaysArticle0004281026000472-s2.0-8503536260150051412929197639Pharmacology & pharmacySesquiterpene; Pristimerin; MaytenusCaspase 3Caspase 7Microtubule associated proteinMicrotubule associated protein 1A 1B light chain 3BPhosphatidylinositol 3 kinasePristimerinProtein bcl 2Sequestosome 1Unclassified drugAntineoplastic agentBiological productPristimerinTriterpeneAnimal cellAnimal experimentAnimal modelAnimal tissueAntineoplastic activityAntiproliferative activityApoptosisArticleATPase activity assayAutophagyBreast cancerCancer stem cellCell vacuoleControlled studyDrug cytotoxicityDrug dose comparisonDrug efficacyDrug mechanismEndoplasmic reticulum stressEnzyme activationFemaleFlow cytometryHumanHuman cellIC50In vitro studyIn vivo studyMCF-7 cell lineMouseNonhumanPriority journalProtein cleavageProtein expressionTumor xenograftUnfolded protein responseWestern blottingAnimalApoptosisAutophagyCancer stem cellDrug effectDrug screeningExperimental mammary neoplasmTumor cell line