Zoledronic acid in combination with serine/threonine phosphatase inhibitors induces enhanced cytotoxicity and apoptosis in hormone-refractory prostate cancer cell lines by decreasing the activities of PP1 and PP2A

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dc.contributor.authorCirak Y.
dc.contributor.authorVarol U.
dc.contributor.authorAtmaca H.
dc.contributor.authorKisim A.
dc.contributor.authorSezgin C.
dc.contributor.authorKarabulut B.
dc.contributor.authorUzunoglu S.
dc.contributor.authorUslu R.
dc.contributor.authorKaraca B.
dc.date.accessioned2024-07-22T08:19:07Z
dc.date.available2024-07-22T08:19:07Z
dc.date.issued2012
dc.description.abstractOBJECTIVES • To investigate if the cytotoxic and apoptotic effect of zoledronic acid (ZA) can be enhanced by the addition of the serine/threonine protein phosphatase inhibitors calyculin A (CA) and okadaic acid (OA) in hormone and drug refractory prostate cancer cells, PC-3 and DU-145. • To discover the effect of these combination treatments on phosphatase 1 (PP1) and PP2A protein expression levels in prostate cancer cells. MATERIALS AND METHODS • An XTT cell viability assay was used to determine cytotoxicity. • Apoptosis was evaluated by enzymelinked immunosorbent assay (ELISA) using a Cell Death Detection ELISA Plus Kit and verifi ed by measuring caspase 3/7 enzyme activity. • The PP1 and PP2A enzyme activities were evaluated by serine/threonine phosphatase ELISA and expression levels of PP1 and PP2A proteins were then re-assessed by Western blot RESULTS • Combination of ZA with either CA or OA showed synergistic cytotoxicity and apoptosis compared with any agent alone in both PC-3 and DU-145 prostate cancer cells. • The combination of ZA with phosphatase inhibitors resulted in enhanced suppression of both PP1 and PP2A enzyme activity andprotein levels, which was more overt with the ZA/CA combination. CONCLUSION • Results from our study increase the translational potential of our in vitro fi ndings and offer the basic rationale for the design of new combinatory strategies with ZA and phosphatase inhibitors for the treatment of prostate cancer, which may become resistant to conventional therapy. © 2012 B J U I N T E R N A T I O N A L.
dc.identifier.DOI-ID10.1111/j.1464-410X.2012.11392.x
dc.identifier.issn1464410X
dc.identifier.urihttp://akademikarsiv.cbu.edu.tr:4000/handle/123456789/17535
dc.language.isoEnglish
dc.subjectApoptosis
dc.subjectBlotting, Western
dc.subjectBone Density Conservation Agents
dc.subjectCell Line, Tumor
dc.subjectCell Proliferation
dc.subjectDiphosphonates
dc.subjectEnzyme-Linked Immunosorbent Assay
dc.subjectHumans
dc.subjectImidazoles
dc.subjectMale
dc.subjectPhosphoprotein Phosphatases
dc.subjectProstatic Neoplasms
dc.subjectProtein Phosphatase 1
dc.subjectProtein Phosphatase 2
dc.subjectcalyculin A
dc.subjectcaspase 3
dc.subjectcaspase 7
dc.subjectokadaic acid
dc.subjectphosphoprotein phosphatase 1
dc.subjectphosphoprotein phosphatase 2A
dc.subjectzoledronic acid
dc.subjectbisphosphonic acid derivative
dc.subjectbone density conservation agent
dc.subjectimidazole derivative
dc.subjectphosphoprotein phosphatase
dc.subjectphosphoprotein phosphatase 1
dc.subjectphosphoprotein phosphatase 2
dc.subjectzoledronic acid
dc.subjectMLCS
dc.subjectMLOWN
dc.subjectantineoplastic activity
dc.subjectapoptosis
dc.subjectarticle
dc.subjectcancer cell culture
dc.subjectcancer combination chemotherapy
dc.subjectcell viability
dc.subjectconcentration response
dc.subjectcontrolled study
dc.subjectdrug cytotoxicity
dc.subjectdrug potentiation
dc.subjectenzyme activity
dc.subjectenzyme inhibition
dc.subjectenzyme linked immunosorbent assay
dc.subjecthuman
dc.subjecthuman cell
dc.subjectIC 50
dc.subjectin vitro study
dc.subjectmale
dc.subjectmonotherapy
dc.subjectpriority journal
dc.subjectprotein expression
dc.subjectWestern blotting
dc.subjectapoptosis
dc.subjectbiosynthesis
dc.subjectcell proliferation
dc.subjectcomparative study
dc.subjectdrug antagonism
dc.subjectdrug effect
dc.subjectmetabolism
dc.subjectpathology
dc.subjectprostate tumor
dc.subjecttumor cell line
dc.titleZoledronic acid in combination with serine/threonine phosphatase inhibitors induces enhanced cytotoxicity and apoptosis in hormone-refractory prostate cancer cell lines by decreasing the activities of PP1 and PP2A
dc.typeArticle

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