Combination of zoledronic acid and serine/threonine phosphatase inhibitors induces synergistic cytotoxicity and apoptosis in human breast cancer cells via inhibition of PI3K/Akt pathway

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dc.contributor.authorSurmeli Z.
dc.contributor.authorGursoy P.
dc.contributor.authorErdogan A.P.
dc.contributor.authorBozkurt E.
dc.contributor.authorAtmaca H.
dc.contributor.authorUzunoglu S.
dc.contributor.authorSezgin C.
dc.contributor.authorŞanlı U.A.
dc.contributor.authorUslu R.
dc.contributor.authorKaraca B.
dc.date.accessioned2024-07-22T08:12:10Z
dc.date.available2024-07-22T08:12:10Z
dc.date.issued2016
dc.description.abstractThe aim of this study was to investigate the cytotoxic and apoptotic effects of zoledronic acid (ZA) in combination with serine/threonine protein phosphatase inhibitors, calyculin-A (CA) and okadaic acid (OA), in human MCF-7 and MDA-MB-231 breast cancer cells. XTT cell viability assay was used to evaluate cytotoxicity. DNA fragmentation and caspase-3/7 activity assays were performed to evaluate apoptosis. Activities of phosphatase 1 (PP1) and phosphatase 2A (PP2A) were measured by serine/threonine phosphatase ELISA kit. Expression levels of PI3K, p-PI3K, Akt, p-Akt, Bcl-2, p-Bcl-2, Bad, and p-Bad proteins were evaluated by Western blot analysis. Combination of ZA with either CA or OA showed synergistic cytotoxicity and apoptosis as compared to any agent alone in both MCF-7 and MDA-MB-231 breast cancer cells. Combination treatment also resulted in inhibition of both PP1 and PP2A activities. Both agents used alone or in combination did not induce significant changes in total PI3K, Akt, Bcl-2, and Bad expressions, while p-PI3K, p-Akt, p-Bcl-2, and p-Bad levels were reduced by the combination treatment as compared to agents alone. Moreover, apoptotic effect of combination treatment was significantly inhibited in the presence of LY294002, a specific PI3K inhibitor, in both breast cancer cell lines. In conclusion, synergistic apoptotic effect of the combination treatment is correlated with the block of the PI3K/Akt signal pathway in breast cancer cells. © 2015, International Society of Oncology and BioMarkers (ISOBM).
dc.identifier.DOI-ID10.1007/s13277-015-3265-x
dc.identifier.issn10104283
dc.identifier.urihttp://akademikarsiv.cbu.edu.tr:4000/handle/123456789/15947
dc.language.isoEnglish
dc.publisherSpringer Science and Business Media B.V.
dc.subjectApoptosis
dc.subjectBlotting, Western
dc.subjectBreast Neoplasms
dc.subjectCell Line, Tumor
dc.subjectCell Survival
dc.subjectDiphosphonates
dc.subjectDose-Response Relationship, Drug
dc.subjectDrug Synergism
dc.subjectEnzyme Inhibitors
dc.subjectFemale
dc.subjectHumans
dc.subjectImidazoles
dc.subjectMCF-7 Cells
dc.subjectOkadaic Acid
dc.subjectOxazoles
dc.subjectPhosphatidylinositol 3-Kinases
dc.subjectPhosphoprotein Phosphatases
dc.subjectProto-Oncogene Proteins c-akt
dc.subjectSignal Transduction
dc.subject2 morpholino 8 phenylchromone
dc.subjectcalyculin A
dc.subjectcaspase 3
dc.subjectcaspase 7
dc.subjectokadaic acid
dc.subjectphosphatase
dc.subjectphosphatase 1
dc.subjectphosphatase 2A
dc.subjectphosphatidylinositol 3 kinase
dc.subjectprotein BAD
dc.subjectprotein bcl 2
dc.subjectprotein kinase B
dc.subjectunclassified drug
dc.subjectzoledronic acid
dc.subjectbisphosphonic acid derivative
dc.subjectcalyculin A
dc.subjectenzyme inhibitor
dc.subjectimidazole derivative
dc.subjectokadaic acid
dc.subjectoxazole derivative
dc.subjectphosphatidylinositol 3 kinase
dc.subjectphosphoprotein phosphatase
dc.subjectprotein kinase B
dc.subjectzoledronic acid
dc.subjectapoptosis
dc.subjectArticle
dc.subjectbreast cancer cell line
dc.subjectcancer combination chemotherapy
dc.subjectcell viability assay
dc.subjectconcentration response
dc.subjectcontrolled study
dc.subjectDNA fragmentation
dc.subjectdrug cytotoxicity
dc.subjectdrug potentiation
dc.subjectenzyme activity
dc.subjectenzyme inhibition
dc.subjectenzyme linked immunosorbent assay
dc.subjectenzyme phosphorylation
dc.subjecthuman
dc.subjecthuman cell
dc.subjectmonotherapy
dc.subjectpriority journal
dc.subjectprotein expression
dc.subjectprotein phosphorylation
dc.subjectsignal transduction
dc.subjectWestern blotting
dc.subjectantagonists and inhibitors
dc.subjectapoptosis
dc.subjectbreast tumor
dc.subjectcell survival
dc.subjectdose response
dc.subjectdrug effects
dc.subjectdrug potentiation
dc.subjectfemale
dc.subjectMCF-7 cell line
dc.subjectmetabolism
dc.subjectpathology
dc.subjecttumor cell line
dc.titleCombination of zoledronic acid and serine/threonine phosphatase inhibitors induces synergistic cytotoxicity and apoptosis in human breast cancer cells via inhibition of PI3K/Akt pathway
dc.typeArticle

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