2D Gel Electrophoresis based Proteomic analysis reveals that ormeloxifen induces G0-G1 growth arrest and ERK mediated apoptosis in chronic myeloid leukemia cells K562
IR@CDRI: CSIR-Central Drug Research Institute, Lucknow
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| Creator |
Pal, Pooja
Kanaujiya, J K Lochab, Savita Tripathi, S B Bhatt, M L B Singh, P K Sanyal, Sabyasachi Trivedi, A K |
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| Date |
2012-01-03T04:46:43Z
2012-01-03T04:46:43Z 2011 |
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| Identifier |
Proteomics,11(8),1517-1529
http://hdl.handle.net/123456789/746 |
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| Description |
Ormeloxifen is a non-steroidal selective estrogen receptor modulator (SERM) and has been shown to possess anticancer activities in breast and uterine cancer. Here, we show that ormeloxifen induces apoptosis in dose dependent manner in a variety of leukemia cells, more strikingly in K562. 2D-gel electrophoresis of K562 cells induced with ormeloxifen showed that 57% and 30% of proteins belong to apoptosis and cell cycle pathways respectively. Our data demonstrates that ormeloxifen induced apoptosis in K562 cells involves activation of Extracellular Signal-Regulated Kinases (ERK) and subsequent cytochrome-c release leading to mitochondria mediated caspase-3 activation. Ormeloxifen induced apoptosis via ERK activation was drastically inhibited by prior treatment of K562 cells with ERK inhibitor PD98059. Ormeloxifen also inhibits proliferation of K562 cells by blocking them in G0-G1 phase by inhibiting c-myc promoter via ormeloxifen induced MBP-1 (c-myc promoter binding protein) and upregulation of p21 expression. We further show that ormeloxifen induced apoptosis in K562 is translatable to mononuclear cells isolated from Chronic Myeloid Leukemia (CML) patients. Thus, ormeloxifen induces apoptosis in K562 cells via phosphorylation of ERK and arrests them in G0-G1 phase by reciprocal regulation of p21 and c-myc. Therefore, inclusion of ormeloxifen in the therapy of CML can be of potential utility.
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1367291 bytes
1367291 bytes application/pdf application/pdf |
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| Language |
en
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| Relation |
cdricommunicationno.8020
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| Subject |
Ormeloxifen
Apoptosis K562 Myeloid Leukemia ERK MBP-1 Proteomics |
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| Title |
2D Gel Electrophoresis based Proteomic analysis reveals that ormeloxifen induces G0-G1 growth arrest and ERK mediated apoptosis in chronic myeloid leukemia cells K562
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| Type |
Article
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