{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:22:52Z","timestamp":1790281372424,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2009,6,22]],"date-time":"2009-06-22T00:00:00Z","timestamp":1245628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Anatomical Record"],"published-print":{"date-parts":[[2009,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Imatinib mesylate is effective against Ph chromosome\u2010positive leukemia; however, resistance has been reported. High expression of <jats:italic>bcr\u2010abl<\/jats:italic> in mRNA and protein levels, and other alterations were found in patients who experienced imatinib treatment failures and thus it is important to design alternative treatment strategies. The aim of this study was to evaluate the <jats:italic>in vitro<\/jats:italic> effect of berbamine, on imatinib\u2010resistant chronic myelogenous leukemia (CML) K562 (K562\u2010r) cells, and explore the mechanisms. The growth of K562\u2010r cells was examined using the 3\u2010(4,5\u2010dimethylthiazol\u20102yl)\u20102,5\u2010diphenyl\u2010tetrazolium bromide (MTT) assay. Morphological analysis and DNA agarose electrophoresis were used to detect apoptosis in K562\u2010r cells, and the extent of the cells in the sub\u2010G1 cell cycle phase was measured using flow cytometry. The expression levels of BCR\u2010ABL, phospho\u2010BCR\u2010ABL, and nuclear factor \u03baB (NF\u2010\u03baB), I\u03baB\u03b1, phospho\u2010I\u03baB\u03b1, I\u03baB kinases \u03b1(IKK\u03b1), and Survivin were determined by Western blot. <jats:italic>bcr\u2010abl<\/jats:italic> mRNA expression was determined by RT\u2010PCR. MTT assays indicated that berbamine significantly inhibited the proliferation of K562\u2010r cells. Cells with characteristics of apoptosis were confirmed by morphology examination and DNA agarose electrophoresis and percentage of apoptosis were increased after treatment with berbamine. The results also showed that berbamine was able to down\u2010regulate BCR\u2010ABL and phospho\u2010BCR\u2010ABL proteins by affecting <jats:italic>bcr\u2010abl<\/jats:italic> mRNA expression and decrease expression of nuclear NF\u2010\u03baB, phospho\u2010I\u03baB\u03b1, IKK\u03b1, and Survivin. Collectively, berbamine could inhibit the proliferation of K562\u2010r cells and induce apoptosis. The mechanisms may be related at least in part, to inhibit BCR\u2010ABL and its downstream NF\u2010\u03baB signaling. Berbamine may provide an alternative candidate for the treatment of patients with CML resistant to imatinib therapy. Anat Rec, 292:945\u2013950, 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ar.20924","type":"journal-article","created":{"date-parts":[[2009,6,22]],"date-time":"2009-06-22T10:48:57Z","timestamp":1245667737000},"page":"945-950","source":"Crossref","is-referenced-by-count":16,"title":["The Antiproliferation Effect of Berbamine on K562 Resistant Cells by Inhibiting NF\u2010\u03baB Pathway"],"prefix":"10.1002","volume":"292","author":[{"given":"Yan\u2010Lin","family":"Wei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Ying","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,6,22]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21590"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-09-2896"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.11199"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403998"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.10.5531"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-06-094508"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V101.2.690"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200104053441402"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2005.05.004"},{"key":"e_1_2_5_11_1","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1242\/jcs.115.1.141","article-title":"The role of IKK in constitutive activation of NF\u2010\u03ba B transcription factor in prostate carcinoma cells","volume":"115","author":"Gasparian AV","year":"2002","journal-title":"J Cell Sci"},{"key":"e_1_2_5_12_1","first-page":"209","article-title":"Effects of berbamine on growth of leukemia cell line NB4 and its mechanism","volume":"35","author":"He ZW","year":"2006","journal-title":"J Zhejiang Univ (Medical Sci)"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-11-125278"},{"key":"e_1_2_5_14_1","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1182\/blood.V112.11.1095.1095","article-title":"Dasatinib\u2010associated major molecular responses are rapidly achieved in patients with chronic myeloid leukemia in chronic phase (CML\u2010CP) following resistance, suboptimal response, or intolerance on imatinib[abstract]","volume":"112","author":"Hochhaus A","year":"2008","journal-title":"Blood"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-05-092056"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207101"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.7.968"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403241"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1768"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2009.19"},{"key":"e_1_2_5_21_1","first-page":"754","article-title":"Effects of berbamine on Jurkat cells and its mechanisms in vitro and in vivo","volume":"25","author":"Wu D","year":"2004","journal-title":"Chin J Hematol"},{"key":"e_1_2_5_22_1","first-page":"261","article-title":"Berbamine, a calmodulin antagonist, induces apoptosis in human leukemia K562 cells","volume":"24","author":"Xu L","year":"2003","journal-title":"Chin J Hematol"}],"container-title":["The Anatomical Record"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Far.20924","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ar.20924","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T19:25:51Z","timestamp":1759951551000},"score":1,"resource":{"primary":{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/10.1002\/ar.20924"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,6,22]]},"references-count":21,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2009,7]]}},"alternative-id":["10.1002\/ar.20924"],"URL":"https:\/\/doi.org\/10.1002\/ar.20924","archive":["Portico"],"relation":{},"ISSN":["1932-8486","1932-8494"],"issn-type":[{"value":"1932-8486","type":"print"},{"value":"1932-8494","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,6,22]]}}}