Botta, BrunoMori, MattiaBerardozzi, SimoneIngallina, Cinzia2022-10-272022-10-272016-12-25Cevatemre, B. vd. (2016). "The plant-derived triterpenoid tingenin B is a potent anticancer agent due to its cytotoxic activity on cancer stem cells of breast cancer in vitro". Chemico-Biological Interactions, 260, 248-255.0009-27971872-7786https://doi.org/10.1016/j.cbi.2016.10.001https://www.sciencedirect.com/science/article/pii/S0009279716304239http://hdl.handle.net/11452/29246Despite the rapid advances in chemotherapy regimens, the outcome of patients with breast cancer is not satisfactory. One of the reasons of this dissatisfaction is that subsets of cells in tumors which referred as cancer stem cells (CSCs) show and/or gain resistance to therapies. Thus, compounds that target CSCs are urgently needed. Since some are already used in the clinic, natural products have great potential for further development as anti cancer drugs. The aim of this study is to investigate the cytotoxic activity of tingenin b (or 22 beta-hydroxytingenone) which is a quinone-methide triterpenoid structurally related to tingenone, against breast CSCs (stem-cell enriched population from MCF-7 cell line, MCF-7s). It has been found that tingenin b was cytotoxic against MCF-7s (IC50 value for 48 h was found to be 2.38 mu M) by inducing apoptosis. It was evident by Annexin V staining positivity, decreased mitochondria( membrane potential and Bcl-2 dephosphorylation with a concomitant increase in Bax protein expression. In addition, endoplasmic reticulum stress was also found to be involved in tingenin b-induced cell death. In conclusion, the results warrant further studies aimed at elucidating and corroborating its possible use in the treatment of breast cancer.eninfo:eu-repo/semantics/closedAccessBiochemistry & molecular biologyPharmacology & pharmacyToxicologyTingenoneBreastER stressChemotherapyMalignancyMammosphereEndoplasmic-reticulumProspective identificationNatural-productsTissue-culturesUrsolic acidBcl-2 familyStressPristimerinApoptosisSubpopulationAntineoplastic agentsApoptosisBreast neoplasmsCell membraneCell nucleusCell proliferationEndoplasmic reticulum stressHumansMaytenusMCF-7 cellsMicroscopy, fluorescenceMitochondriaNeoplastic stem cellsPhytotherapyTriterpenesArticle0003905154000272-s2.0-8499710905224825526027720947Biochemistry & molecular biologyPharmacology & pharmacyToxicologySesquiterpene; Pristimerin; MaytenusAntineoplastic agentCytokeratin 18Glucose regulated protein 78Nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferaseProtein baxProtein bcl 2Protein IRE1Protein IRE1 alphaTingenin bTranscription factor Sox2TriterpenoidUnclassified drugAntineoplastic agentTingenin BTriterpeneApoptosisApoptosis assayArticleBarkBreast cancer cell lineCell membraneCell viabilityConcentration responseControlled studyDrug cytotoxicityDrug structureEndoplasmic reticulum stressIC50In vitro studyMammosphereMCF 7 cell lineMitochondrial membrane potentialProtein cleavageProtein dephosphorylationProtein expressionTumor spheroidUbiquitinationBreast tumorCancer stem cellCell nucleusCell proliferationChemistryDrug effectsFluorescence microscopyHumanMaytenusMCF-7 cell lineMetabolismMitochondrionPathologyPhytotherapy