Novel ferrocenyl pyrazoles inhibit breast cancer cell viability via induction of apoptosis and inhibition of PI3K/Akt and ERK1/2 signaling

dc.contributor.authorAtmaca H.
dc.contributor.authorÖzkan A.N.
dc.contributor.authorZora M.
dc.date.accessioned2024-07-22T08:10:56Z
dc.date.available2024-07-22T08:10:56Z
dc.date.issued2017
dc.description.abstractDespite 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 Ltd
dc.identifier.DOI-ID10.1016/j.cbi.2016.12.010
dc.identifier.issn00092797
dc.identifier.urihttp://akademikarsiv.cbu.edu.tr:4000/handle/123456789/15457
dc.language.isoEnglish
dc.publisherElsevier Ireland Ltd
dc.subjectApoptosis
dc.subjectBreast Neoplasms
dc.subjectCaspase 3
dc.subjectCell Line, Tumor
dc.subjectCell Proliferation
dc.subjectCell Survival
dc.subjectFemale
dc.subjectFerrous Compounds
dc.subjectHumans
dc.subjectMCF-7 Cells
dc.subjectMicroscopy, Atomic Force
dc.subjectMitogen-Activated Protein Kinase 1
dc.subjectMitogen-Activated Protein Kinase 3
dc.subjectPhosphatidylinositol 3-Kinases
dc.subjectProto-Oncogene Proteins c-akt
dc.subjectPyrazoles
dc.subjectSignal Transduction
dc.subject5 ferrocenyl 1 phenyl 1h pyrazole
dc.subject5 ferrocenyl 1h pyrazole
dc.subjectcaspase 3
dc.subjectmitogen activated protein kinase 1
dc.subjectmitogen activated protein kinase 3
dc.subjectphosphatidylinositol 3 kinase
dc.subjectprotein kinase B
dc.subjectpyrazole derivative
dc.subjectunclassified drug
dc.subjectcaspase 3
dc.subjectferrocene
dc.subjectferrous ion
dc.subjectmitogen activated protein kinase 1
dc.subjectmitogen activated protein kinase 3
dc.subjectphosphatidylinositol 3 kinase
dc.subjectprotein kinase B
dc.subjectpyrazole derivative
dc.subjectapoptosis
dc.subjectArticle
dc.subjectatomic force microscopy
dc.subjectbreast cancer cell line
dc.subjectbreast epithelium cell
dc.subjectcancer cell line
dc.subjectcell death
dc.subjectcell ultrastructure
dc.subjectcell viability
dc.subjectconcentration (parameters)
dc.subjectcontrolled study
dc.subjectcytotoxicity
dc.subjectDNA fragmentation assay
dc.subjectdrug structure
dc.subjectenzyme inhibition
dc.subjecthuman
dc.subjecthuman cell
dc.subjectMCF 10A cell line
dc.subjectMCF-7 cell line
dc.subjectphase contrast microscope
dc.subjectsignal transduction
dc.subjectXTT assay
dc.subjectapoptosis
dc.subjectbreast tumor
dc.subjectcell proliferation
dc.subjectcell survival
dc.subjectchemistry
dc.subjectdrug effects
dc.subjectfemale
dc.subjectmetabolism
dc.subjectpathology
dc.subjectsignal transduction
dc.subjecttumor cell line
dc.titleNovel ferrocenyl pyrazoles inhibit breast cancer cell viability via induction of apoptosis and inhibition of PI3K/Akt and ERK1/2 signaling
dc.typeArticle

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