Gunel N.S.Yildirim N.Ozates N.P.Oktay L.M.Bagca B.G.Sogutlu F.Ozsaran A.Korkmaz M.Biray Avci C.2024-07-222024-07-22202313570560http://akademikarsiv.cbu.edu.tr:4000/handle/123456789/12431After revealing the anti-cancer properties of boron, which is included in the category of essential elements for human health by the World Health Organization, the therapeutic potential of boron compounds has been begun to be evaluated, and its molecular effect mechanisms have still been among the research subjects. In ovarian cancer, mutations or amplifications frequently occur in the PI3K/Akt/mTOR pathway components, and dysregulation of this pathway is shown among the causes of treatment failure. In the present study, it was aimed to investigate the anti-cancer properties of boron-containing DPD in SKOV3 cells, which is an epithelial ovarian cancer model, through PI3K/AKT/mTOR pathway. The cytotoxic activity of DPD in SKOV3 cells was evaluated by WST-1 test, apoptotic effect by Annexin V and JC-1 test. The gene expressions associated with PI3K/AKT/mTOR pathway were determined by real-time qRT-PCR. In SKOV3 cells, the IC50 value of DPD was found to be 6.7 mM, 5.6 mM, and 5.2 mM at 24th, 48th and 72nd hour, respectively. Compared with the untreated control group, DPD treatment was found to induce apoptosis 2.6-fold and increase mitochondrial membrane depolarization 4.5-fold. DPD treatment was found to downregulate PIK3CA, PIK3CG, AKT2, IGF1, IRS1, MAPK3, HIF-1, VEGFC, CAB39, CAB39L, STRADB, PRKAB2, PRKAG3, TELO2, RICTOR, MLST8, and EIF4B genes and upregulate TP53, GSK3B, FKBP8, TSC2, ULK1, and ULK2 genes. These results draw attention to the therapeutic potential of DPD, which is frequently exposed in daily life, in epithelial ovarian cancer and show that it can be a candidate compound in combination with chemotherapeutics. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.EnglishAll Open Access; Green Open AccessAntigens, NeoplasmAntineoplastic AgentsApoptosisApoptosis Regulatory ProteinsBoronCarcinoma, Ovarian EpithelialCell Line, TumorCell ProliferationFemaleHumansOvarian NeoplasmsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSignal TransductionTOR Serine-Threonine Kinasesapoptosis inducing factorboron derivativecytostatic agentcytotoxic agentdisodium pentaborate decahydrateglycogen synthase kinase 3betahypoxia inducible factor 1initiation factor 4Binsulin receptor substrate 1lipocortin 5mammalian target of rapamycinmitogen activated protein kinase 3phosphatidylinositol 3 kinaseprotein kinase Bprotein kinase B betaprotein p53rapamycin-insensitive companion of mTORserine threonine protein kinase ULK1somatomedin Ctarget of rapamycin complex subunit LST8tuberinunclassified drugvasculotropin Cantineoplastic agentapoptosis regulatory proteinboronCAB39L protein, humanphosphatidylinositol 3 kinaseprotein kinase Bsodium pentaboratetarget of rapamycin kinasetumor antigenAkt signalingantineoplastic activityapoptosisArticlecell membrane depolarizationcontrolled studycytostasisdown regulationdrug cytotoxicityfemalegene expressiongene expression profilinghumanhuman cellIC50mitochondrial membraneovary cancerproapoptotic activityreal time reverse transcription polymerase chain reactionSK-OV-3 cell lineupregulationWST-1 assaycell proliferationgeneticsmetabolismovary tumorsignal transductiontumor cell lineArticle10.1007/s12032-022-01870-1