{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T04:51:54Z","timestamp":1771303914410,"version":"3.50.1"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T00:00:00Z","timestamp":1612396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005851","name":"Shahid Beheshti University of Medical Sciences","doi-asserted-by":"publisher","award":["22091"],"award-info":[{"award-number":["22091"]}],"id":[{"id":"10.13039\/501100005851","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biology International"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although the identification of tyrosine kinase inhibitors (TKIs) has changed the treatment paradigm of many cancer types including chronic myeloid leukemia (CML), still adjustment of neoplastic cells to cytotoxic effects of anticancer drugs is a serious challenge. In the area of drug resistance, epigenetic alterations are at the center of attention and the present study aimed to evaluate whether blockage of epigenetics mechanisms using a pan\u2010histone deacetylase (HDAC) inhibitor induces cell death in CML\u2010derived K562 cells. We found that the abrogation of HDACs using panobinostat resulted in a reduction in survival of the K562 cell line through p27\u2010mediated cell cycle arrest. Noteworthy, the results of the synergistic experiments revealed that HDAC suppression could be recruited as a way to potentiate cytotoxicity of Imatinib and to enhance the therapeutic efficacy of CML. Here, we proposed for the first time that the inhibitory effect of panobinostat was overshadowed, at least partially, through the aberrant activation of the phosphoinositide 3\u2010kinase (PI3K)\/c\u2010Myc axis. Meanwhile, we found that upon blockage of autophagy and the proteasome pathway, as the main axis involved in the activation of autophagy, the anti\u2010leukemic property of the HDAC inhibitor was potentiated. Taken together, our study suggests the beneficial application of HDAC inhibition in the treatment strategies of CML; however, further in vivo studies are needed to determine the efficacy of this inhibitor, either as a single agent or in combination with small molecule inhibitors of PI3K and\/or c\u2010Myc in this malignancy.<\/jats:p>","DOI":"10.1002\/cbin.11557","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T08:12:34Z","timestamp":1611735154000},"page":"1111-1121","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Abrogation of histone deacetylases (HDACs) decreases survival of chronic myeloid leukemia cells: New insight into attenuating effects of the PI3K\/c\u2010Myc axis on panobinostat cytotoxicity"],"prefix":"10.1002","volume":"45","author":[{"given":"Sara","family":"Zehtabcheh","sequence":"first","affiliation":[{"name":"Department of Hematology and Blood Banking, School of Allied Medical Sciences Shahid Beheshti University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amir\u2010Mohammad","family":"Yousefi","sequence":"additional","affiliation":[{"name":"Department of Hematology and Blood Banking, School of Allied Medical Sciences Shahid Beheshti University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sina","family":"Salari","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hematology and Bone Marrow Transplantation, Taleghani Hospital Shahid Beheshti University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Majid","family":"Safa","sequence":"additional","affiliation":[{"name":"Department of Hematology and Blood Banking, Faculty of Allied Medicine Iran University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Majid","family":"Momeny","sequence":"additional","affiliation":[{"name":"Turku Centre for Biotechnology University of Turku and \u00c5bo Akademi University  Turku Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seyed H.","family":"Ghaffari","sequence":"additional","affiliation":[{"name":"Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, School of Medicine Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8029-4920","authenticated-orcid":false,"given":"Davood","family":"Bashash","sequence":"additional","affiliation":[{"name":"Department of Hematology and Blood Banking, School of Allied Medical Sciences Shahid Beheshti University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,2,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/82_2017_6"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0000000000000591"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010716-105106"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.20460"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph3082674"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2019.00136"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.11507"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14442"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2001.tb02153.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI35721"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2008.11.004"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2018.02.013"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.159"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-015-0388-8"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0158208"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers6031769"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2010.04.001"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-03-0849"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-018-0654-9"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/164_2017_81"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncoscience.412"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/10799893.2020.1853159"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173050"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2010.08301.x"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2020.105734"},{"key":"e_1_2_7_27_1","first-page":"769","article-title":"Expression profile of class I histone deacetylases in human cancer tissues","volume":"18","author":"Nakagawa M.","year":"2007","journal-title":"Oncology Reports"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/07357907.2019.1651328"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2010.06.005"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2018.10.036"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-01964-1"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867326666190712160842"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.172411"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.2217\/nnm-2017-0184"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.11322"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-0072"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2017.03.002"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.264"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568026619666181210152115"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0000000000000403"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-011-1364-y"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-12-1242"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2017.04.004"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2017.12.030"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2016.10.057"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-0171"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205942"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.26780"}],"container-title":["Cell Biology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbin.11557","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbin.11557","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbin.11557","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T13:10:12Z","timestamp":1693573812000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cbin.11557"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,4]]},"references-count":47,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["10.1002\/cbin.11557"],"URL":"https:\/\/doi.org\/10.1002\/cbin.11557","archive":["Portico"],"relation":{},"ISSN":["1065-6995","1095-8355"],"issn-type":[{"value":"1065-6995","type":"print"},{"value":"1095-8355","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,4]]},"assertion":[{"value":"2020-09-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}