Bulut G.Atmaca H.Karaca B.2024-07-222024-07-22201914796694http://akademikarsiv.cbu.edu.tr:4000/handle/123456789/14648Aim: AT-101 is a polyphenolic compound with potent anti-apoptotic effects in various cancers. In this study, the possible synergistic cytotoxic and apoptotic effect of trastuzumab/AT-101 combination was investigated in HER2-positive breast cancer cell lines. Materials & methods: SKBR-3, MDA-MB-453 and MCF-10A cell lines were treated with a trastuzumab/AT-101 combination. Synergistic cytotoxicity and apoptosis effects were shown and then PI3K and Akt protein levels were studied. Result: The trastuzumab/AT-101 combination induced synergistic cytotoxicity and apoptosis in both breast cancer cells but not in MCF-10A cells. Combination treatment induced cytotoxicity via inhibiting PI3K/AKT but not the MAPK/ERK pathway. Conclusion: The trastuzumab/AT-101 combination may be a good candidate for patients with trastuzumab-resistant Her2-positive breast cancer and inhibition of the PI3K/AKT pathway may be one of the underlying mechanisms. © 2019 Gulcan Bulut, Harika Atmaca & Burcak Karaca.EnglishAll Open Access; Hybrid Gold Open AccessAntineoplastic Agents, ImmunologicalAntineoplastic Agents, PhytogenicAntineoplastic Combined Chemotherapy ProtocolsApoptosisBreast NeoplasmsCell Line, TumorDrug Screening Assays, AntitumorDrug SynergismFemaleGossypolHumansPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReceptor, ErbB-2Signal TransductionTrastuzumabisosorbidemitogen activated protein kinasephosphatidylinositol 3 kinaseprotein kinase Btrastuzumabantineoplastic agentepidermal growth factor receptor 2ERBB2 protein, humangossypolgossypol acetic acidimmunological antineoplastic agentphosphatidylinositol 3 kinaseprotein kinase BtrastuzumabapoptosisArticlebreast cancercancer cellcontrolled studycytotoxicitydrug effectdrug inhibitiondrug mechanismdrug potentiationhumanhuman cellMCF-10A cell lineMDA-MB-453 cell linepriority journalsignal transductionSK-BR-3 cell lineapoptosisbreast tumordrug screeningfemalemetabolismpathologytumor cell lineTrastuzumab in combination with AT-101 induces cytotoxicity and apoptosis in Her2 positive breast cancer cellsArticle10.2217/fon-2019-0521