Prostat kanseri hücre hatlarında protein fosfataz inhibitörleri ve zoledronik asit uygulamasının aditif sinerjistik antitümöral etkileri.
Küçük Resim Yok
Tarih
2011
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Zoledronik asit ve serin/treonin protein fosfataz inhibitörleri (okadaik asit ve kalikulin A)'nin sitotoksik ve apoptotik etkileri bir çok hücre hatında incelenmiş olmakla birlikte etki mekanizmaları tam olarak bilinmemektedir.Literatürde zoledronik asidin sitotoksik apoptotik etkileri sırasında serin treonin protein fosfataz sisteminin rolünün incelendiği çalışma bulunmamaktadır.Biz çalışmamızda serin treonin protein fosfataz inhibitörleri ile oluşturulan sitoplazmik hiperfosforile durmda, zoledronik asidin sitotoksik apoptotik etkilerinin değişip değişmediğini araştırdık.Sitotoksisite taini için XTT metodu kullanıldı. Apoptosis ELİSA yöntemi ile değerlendirildi ve kaspaz 3/7 enzim aktivitesi ölçümü ile doğrulandı. Hem zoledronik asit hem de protein fosfataz inhibitörlerinin PC3 ve DU145 prostat kanser hücre hatlarında doz ve zamana bağlı artan sitotoksik ve apoptotik etkileri tespit edildi. Deney ortamına farnesol ve geranilgeraniol ilavesi ile zoledronik asitin sitotoksik etkisinin kaybolduğu saptandı.Zoledronik asidin protein fosfataz inhibitörleri ile kombinasyonunda kuvetli sinerjistik sitotoksik ve apoptotik etki gözlendi.Sonuç olarak protein fosfataz enzim sisteminin'nın zoledronik asidin sitotoksik apoptotik etkileri sırasında oldukça önemli olduğunu söyleyebiliriz
The cytotoxic and apoptotic effects of Zoledronic acid and serine / threonine proteine phosphatase inhibitors (ocadaic acid and calyculin A) had been suggested in a considerable numbre of cell line. But exact mechanisim underling their cytotoxic and apoptotic effects remains unclear. There is almost no data on the relevance of serine/threonine protein phosphatase system in the zoledronic acid induced cytotoxicity and apoptosis. In this study we investigated wether cytotoxic and apoptotic effects of zoledronic acid in DU145 and PC3 cell lines changes in cytosolic hiperfosforile status mediated by serine/threonine proteine phosphatase inhibitors. Trypan blue dye exclusion test and MTT assay were utilised for determining cytotoxicity. Apoptosis was evaluated by enzyme-linked immunosorbent assay (ELISA) using Cell Death Detection ELISA Plus Kit. Moreover was verified by measuring caspase 3/7 enzyme activity. Time- and dose-dependent increases in cytotoxic and apoptotic effects on PC-3 and DU-145 cells were observed in response to both zoledronic acid and serine/threonine proteine phosphatase inhibitors (okadaic acid and calyculin A). Adittion of fernasol and geranilgeraniol to experiment medium completely blocked PC-3 and DU-145 growth inhibition induced by the zoledronic acid. In combination of zoledronic acid by both okadaic acid and calyculin A strong sinergysim was observed. In conclusion,serine/ threonine protein phosphatase system plays a role in zoledronic acid induced cytotoxicity and apoptosis of DU145 and PC3 cells and should be investigated as a new window furthermore.
The cytotoxic and apoptotic effects of Zoledronic acid and serine / threonine proteine phosphatase inhibitors (ocadaic acid and calyculin A) had been suggested in a considerable numbre of cell line. But exact mechanisim underling their cytotoxic and apoptotic effects remains unclear. There is almost no data on the relevance of serine/threonine protein phosphatase system in the zoledronic acid induced cytotoxicity and apoptosis. In this study we investigated wether cytotoxic and apoptotic effects of zoledronic acid in DU145 and PC3 cell lines changes in cytosolic hiperfosforile status mediated by serine/threonine proteine phosphatase inhibitors. Trypan blue dye exclusion test and MTT assay were utilised for determining cytotoxicity. Apoptosis was evaluated by enzyme-linked immunosorbent assay (ELISA) using Cell Death Detection ELISA Plus Kit. Moreover was verified by measuring caspase 3/7 enzyme activity. Time- and dose-dependent increases in cytotoxic and apoptotic effects on PC-3 and DU-145 cells were observed in response to both zoledronic acid and serine/threonine proteine phosphatase inhibitors (okadaic acid and calyculin A). Adittion of fernasol and geranilgeraniol to experiment medium completely blocked PC-3 and DU-145 growth inhibition induced by the zoledronic acid. In combination of zoledronic acid by both okadaic acid and calyculin A strong sinergysim was observed. In conclusion,serine/ threonine protein phosphatase system plays a role in zoledronic acid induced cytotoxicity and apoptosis of DU145 and PC3 cells and should be investigated as a new window furthermore.
Açıklama
Anahtar Kelimeler
Onkoloji, Oncology, Fosforik monoester hidrolazlar, Phosphoric monoester hydrolases, Neoplazmlar, Neoplasms, Prostat, Prostate, Prostat neoplazmları, Prostatic neoplasms, Sinerji, Synergy, Zoledronik asit, Zoledronic acid, İnhibitör, Inhibitor
