{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T05:59:26Z","timestamp":1760853566199,"version":"build-2065373602"},"reference-count":16,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2011,10,26]],"date-time":"2011-10-26T00:00:00Z","timestamp":1319587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We previously isolated aaptamine, a benzonaphthyridine alkaloid, from marine sponge Aaptos suberitoids. In this study, we investigated the anti-proliferative effect of aaptamine on chronic myeloid leukemia (CML) K562 cells. Aaptamine inhibited growth of K562 with a GI50 as 10 \u03bcM, and arrested cell cycle at G2\/M phase. Western blot analysis indicated that aaptamine induced p21 expression in K562 cells. Moreover, p21 promoter was activated by aaptamine treatment in p21 transfected K562 cells. Since K562 is p53 negative, aaptamine was demonstrated to be a p53-independent p21 inducer in CML cells.<\/jats:p>","DOI":"10.3390\/ijms12117352","type":"journal-article","created":{"date-parts":[[2011,10,26]],"date-time":"2011-10-26T11:27:26Z","timestamp":1319628446000},"page":"7352-7359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Antiproliferative Effect of Aaptamine on Human Chronic Myeloid Leukemia K562 Cells"],"prefix":"10.3390","volume":"12","author":[{"given":"Meihua","family":"Jin","sequence":"first","affiliation":[{"name":"Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmaceutical Sciences and Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wennan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmaceutical Sciences and Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmaceutical Sciences and Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Motomasa","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongquan","family":"Duan","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmaceutical Sciences and Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dexin","family":"Kong","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmaceutical Sciences and Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2011,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1038\/300765a0","article-title":"A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemia","volume":"300","author":"Grosveld","year":"1982","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1182\/asheducation-2010.1.122","article-title":"Chronic myeloid leukemia 2010: Where are we now and where can we go?","volume":"2010","author":"Radich","year":"2010","journal-title":"Hematology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/S0092-8674(03)00190-9","article-title":"Mechanisms of autoinhibition and STI-571\/imatinib resistance revealed by mutagenesis of BCR-ABL","volume":"112","author":"Azam","year":"2003","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.canlet.2006.07.010","article-title":"Resistance to imatinib mesylate in chronic myeloid leukaemia","volume":"249","author":"Melo","year":"2007","journal-title":"Cancer Lett"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1097\/00062752-200401000-00006","article-title":"Mechanisms and implications of imatinib resistance mutations in BCR-ABL","volume":"11","author":"Nardi","year":"2004","journal-title":"Curr. 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