Atmaca H.Özkan A.N.Zora M.2024-07-222024-07-22201700092797http://akademikarsiv.cbu.edu.tr:4000/handle/123456789/15457Despite the advances in early detection and targeted therapies, chemotherapy is still of vital importance in breast cancer treatment. However, development of drug resistance and serious side effects limits their usage. Thus, there is an urgent need for safer and more effective agents against breast cancer. We have previously described the synthesis of a number of pyrazole derivatives, and in the current study, we have investigated the effects of two different ferrocenyl pyrazole (FP) derivates, 5-ferrocenyl-1-phenyl-1H-pyrazole (FP-Ph) and 5-ferrocenyl-1H-pyrazole (FP-H), on breast cancer cells. First, we investigated the effects of both FPs on cell viability and induction of cell death in breast cancer cells and benign MCF-10A cells by XTT and DNA fragmentation assays, respectively. Morphological changes in human breast cancer cells after FPs treatment were detected by both phase contrast microscope and atomic force microscopy (AFM). Then, we tested whether FPs exert their cytotoxic effect through inhibiting PI3K/Akt and/or ERK1/2 signaling pathways by using specific inhibitors. Both FPs induced cytotoxicity in a time and concentration-dependent manner in breast cancer cells; however, MCF-10A benign breast epithelial cells were much less susceptible to the cytotoxic effect of both FPs. FPs inhibited both PI3K/Akt and ERK 1/2 signaling pathways in breast cancer cells. The ultra structure images of MCF-7 cells by AFM showed that the cell surface was smooth in untreated cells, but it was rough with protrusions in treated cells. Both FPs induced apoptotic cell death in MDA-MB-231 cells; however, necrotic cell death was induced in caspase-3 lack MCF-7 cells, which implies that the synthesized FPs may induce apoptosis through caspase-3 dependent mechanism. In summary, these results suggest that FPs might be promising agents for the breast cancer therapy. © 2016 Elsevier Ireland LtdEnglishApoptosisBreast NeoplasmsCaspase 3Cell Line, TumorCell ProliferationCell SurvivalFemaleFerrous CompoundsHumansMCF-7 CellsMicroscopy, Atomic ForceMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Phosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktPyrazolesSignal Transduction5 ferrocenyl 1 phenyl 1h pyrazole5 ferrocenyl 1h pyrazolecaspase 3mitogen activated protein kinase 1mitogen activated protein kinase 3phosphatidylinositol 3 kinaseprotein kinase Bpyrazole derivativeunclassified drugcaspase 3ferroceneferrous ionmitogen activated protein kinase 1mitogen activated protein kinase 3phosphatidylinositol 3 kinaseprotein kinase Bpyrazole derivativeapoptosisArticleatomic force microscopybreast cancer cell linebreast epithelium cellcancer cell linecell deathcell ultrastructurecell viabilityconcentration (parameters)controlled studycytotoxicityDNA fragmentation assaydrug structureenzyme inhibitionhumanhuman cellMCF 10A cell lineMCF-7 cell linephase contrast microscopesignal transductionXTT assayapoptosisbreast tumorcell proliferationcell survivalchemistrydrug effectsfemalemetabolismpathologysignal transductiontumor cell lineArticle10.1016/j.cbi.2016.12.010