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Here, we show that ormeloxifen induces apoptosis in dose\u2010dependent manner in a variety of leukemia cells, more strikingly in K562. 2\u2010DE\u2010gel electrophoresis of K562 cells induced with ormeloxifen showed that 57 and 30% of proteins belong to apoptosis and cell\u2010cycle pathways, respectively. Our data demonstrate that ormeloxifen\u2010induced apoptosis in K562 cells involves activation of extracellular signal\u2010regulated kinases (ERKs) and subsequent cytochrome <jats:italic>c<\/jats:italic> release, leading to mitochondria\u2010mediated caspase\u20103 activation. Ormeloxifen\u2010induced 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\u2013G1 phase by inhibiting c\u2010myc promoter via ormeloxifen\u2010induced MBP\u20101 (c\u2010myc promoter\u2010binding protein) and upregulation of p21 expression. We further show that ormeloxifen\u2010induced 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\u2013G1 phase by reciprocal regulation of p21 and c\u2010myc. Therefore, inclusion of ormeloxifen in the therapy of chronic myeloid leukemia can be of potential utility.<\/jats:p>","DOI":"10.1002\/pmic.201000720","type":"journal-article","created":{"date-parts":[[2011,2,14]],"date-time":"2011-02-14T03:42:27Z","timestamp":1297654947000},"page":"1517-1529","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["2\u2010D gel electrophoresis\u2010based proteomic analysis reveals that ormeloxifen induces G0\u2013G1 growth arrest and ERK\u2010mediated apoptosis in chronic myeloid leukemia cells K562"],"prefix":"10.1002","volume":"11","author":[{"given":"Pooja","family":"Pal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jitendra K.","family":"Kanaujiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savita","family":"Lochab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shashi B.","family":"Tripathi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madan L. 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