{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:56:20Z","timestamp":1790884580529,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T00:00:00Z","timestamp":1679529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biology International"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ormeloxifene (ORM) (3,4\u2010trans\u20102,2\u2010dimethyl\u20103\u2010phenyl\u20104\u2010p\u2010(\u03b2\u2010pyrrolidinoethoxy) phenyl\u20107\u2010methoxychroman), world's first nonsteroidal selective estrogen receptor modulator\u00a0approved for contraception in India has been shown to have potential anticancer activities. Here, we show that ORM\u00a0can induce megakaryocyte and myeloid (granulocytic) but not erythroid differentiation in multipotent human myeloid leukemia cell line K562. We show that ORM at an IC50 of 7.5\u2009\u00b5M can induce morphological changes similar to megakaryocytes in K562 cells. ORM led to increase in levels of megakaryocytic differentiation markers (CD41 and CD61) as well as key transcription factors GATA1 and AML1. We further show that ORM induces megakaryocytic differentiation in K562 cells through ERK activation and induction of autophagy in a fashion similar to other known inducers of megakaryocytic differentiation such as phorbol esters. In addition, as shown earlier, we yet again observed that ORM led to activation of caspases since their inhibition through pan\u2010caspase inhibitor mitigated megakaryocytic differentiation as they led to significant decrease in CD41 and CD61. Because induction of megakaryocytic differentiation in K562 involves growth arrest and exit from cell cycle, we also observed an increase in levels of p21 and p27 with decrease in c\u2010Myc protein levels in K562 cells treated with 7.5\u2009\u00b5M ORM for 24 and 48\u2009h,\u00a0respectively. Taken together, these findings indicate that ORM can markedly induce megakaryocytic differentiation in K562 cells.<\/jats:p>","DOI":"10.1002\/cbin.12017","type":"journal-article","created":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T07:23:42Z","timestamp":1679556222000},"page":"1247-1258","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Ormeloxifene, a nonsteroidal antifertility drug promotes megakaryocyte differentiation in leukemia cell line K562"],"prefix":"10.1002","volume":"47","author":[{"given":"Mukul","family":"Mishra","sequence":"first","affiliation":[{"name":"Division of Cancer Biology CSIR\u2010Central Drug Research Institute (CSIR\u2010CDRI) Lucknow Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil Kumar","family":"Singh","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology CSIR\u2010Central Drug Research Institute (CSIR\u2010CDRI) Lucknow Uttar Pradesh India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gatha","family":"Thacker","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology CSIR\u2010Central Drug Research Institute (CSIR\u2010CDRI) Lucknow Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishal","family":"Upadhyay","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology CSIR\u2010Central Drug Research Institute (CSIR\u2010CDRI) Lucknow Uttar Pradesh India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabyasachi","family":"Sanyal","sequence":"additional","affiliation":[{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad India"},{"name":"Biochemistry and Structural Biology Division CSIR\u2010Central Drug Research Institute (CSIR\u2010CDRI) Lucknow Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6316-0947","authenticated-orcid":false,"given":"Arun Kumar","family":"Trivedi","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology CSIR\u2010Central Drug Research Institute (CSIR\u2010CDRI) Lucknow Uttar Pradesh India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-11-4065"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2015.01.001"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-06-077891"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.5.8.9889"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2010.01416.x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-09-2708"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-11-3550"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/mutage\/14.6.613"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-1053"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.10426"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-11-058941"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2019.10.009"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2009.7"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0b013e3283366bf4"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002866200"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0145-2126(87)90065-8"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2008.86"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-20-0268"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910430506"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(90)90033-7"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-02-205062"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2015.04.012"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201000720"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-009-0290-3"},{"key":"e_1_2_9_26_1","first-page":"1029","article-title":"Effect of soluble CD40L on leukemia K562 cells and its mechanism","volume":"24","author":"Ren M. 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