Involvement of protein phosphatase 2A in interferon-α-2b-induced apoptosis in K562 human chronic myelogenous leukaemia cells
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- 作者：Saydam ; Guray ; Hakan Aydin ; Hikmet ; Sahin ; Fahri ; Selvi ; Nur ; Oktem ; Gulperi ; Terzioglu ; Ender ; et. al.
- 关键词：IFN-α ; interferon alpha ; PP2A ; protein phosphatase type 2A ; OKA ; okadaic acid ; Cal A ; calyculin A ; Interferon-α ; -2b ; Apoptosis ; PP2A ; K562 cells
- 刊名：Leukemia Research
- 出版年：2003
- 出版时间：August, 2003
- 年：2003
- 卷：27
- 期：8
- 页码：709-717
- 全文大小：204 K
文摘
Interferon-alpha (IFN-α)-2b is known to have antiproliferative effects on hematological malignant cells, especially chronic myelogenous leukaemia (CML). However, it can induce cytogenetical remissions in a very small percentage of the patients. Also during interferon therapy, resistance can emerge in the CML clones. K562 is an in vitro model cell line transformed from a Ph positive CML patient. It can be induced to differentiate to granulocytic and/or monocytic lineages with certain molecules. IFN-α-2b generally exerts its effects on CML cells by Janus family kinases (Jak/Stat) pathway, mostly through tyrosine kinase system. However, there is almost no data on the relevance of serine/threonine (Ser/Thr) protein phosphatase (PP) system in the interferon induced signal transduction pathways. In this study, we investigated serine/threonine protein phosphatases in the IFN-α-2b induced K562 cytotoxicity. Trypan blue dye exclusion test and MTT assay were utilised for determining cytotoxicity. IC50 of IFN-α-2b on K562 cells was found to be 600IU/ml. However, no differentiation was determined by analysis of cell surface antigen expressions. Serine/threonine protein phosphatase inhibitors calyculin A (Cal A) and okadaic acid (OKA) augmented the IFN-α-2b induced cytotoxicity. Apoptosis assay by the mono-oligonucleosome detection and acridine orange/propidium iodide dye revealed marked apoptosis underlying cytotoxicity. Phosphatase enzyme assay revealed a gradual increase in protein phosphatase 2A (PP2A) activity during interferon induced cytotoxicity. Conversely, immunoblots showed no change in the expression of PP2A catalytic and regulatory subunits. In conclusion, PP2A plays a role in IFN-α-2b induced apoptosis of K562 cells and should be investigated as a new window furthermore.