{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:56:08Z","timestamp":1753869368547,"version":"3.41.2"},"reference-count":45,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T00:00:00Z","timestamp":1659484800000},"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":["J Biochem &amp; Molecular Tox"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Despite advances in cancer treatment, chronic myeloid leukemia (CML) is still one of the leading causes of death in the world. Due to the role of inflammation in cancer promotion and progression, thus use of anti\u2010inflammatory agents may suppress cancer cell growth. In this study, we used two anti\u2010inflammatory drugs, cilostazol and meloxicam, for the treatment of CML. Cell viability was measured using 3\u2010(4,5\u2010dimethylthiazol\u20102\u2010yl)\u20102,5\u2010diphenyltetrazolium bromide (MTT) assay and the synergism occurrence was calculated by compusyn software. Annexin V\/PI test and Hoechst staining were used to determine the apoptosis rate. To determine the pathway of apoptosis induction, the expression of BCL2 Associated X (Bax) and B\u2010cell lymphoma\u20102 (Bcl\u20102) apoptotic genes and caspases activity were evaluated. The cell cycle was analyzed by propidium iodide (PI) staining and flow cytometry. Western blot analysis and immunofluorescence were performed to estimate alterations in Ak strain transforming\u20101 (AKT\u20101), phosphprylated AKT\u20101 (p\u2010AKT\u20101), adenosine mono\u2010phosphate\u2010kinase (AMPK), and phosphorylated AMPK (p\u2010AMPK) proteins and BCR\/ABL and c\u2010Myc distribution, respectively. Results showed that cilostazol, meloxicam, and their combination drug reduced cell viability (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Compared with control, expression of Bax and Bcl\u20102 decreased in treated cells, respectively (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). The caspase\u20109 activity increased in treated cells compared to control cells (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001<jats:italic>).<\/jats:italic> The applied drugs decreased the protein level of p\u2010AKT\u20101 while increasing the p\u2010AMPK protein level (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). BCR\/ABL and c\u2010Myc Protein distribution significantly decreased in treated cells. In conclusion, the combination drug had more cytotoxic effects than cilostazol and meloxicam alone and induced apoptosis by inhibiting AKT\u20101 activation and c\u2010Myc reduction. Therefore using combination drugs effectively can treat cancers of CML origin.<\/jats:p>","DOI":"10.1002\/jbt.23185","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T11:39:57Z","timestamp":1659526797000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Inhibiting AKT signaling pathway with cilostazol and meloxicam synergism for suppressing K562 cells in vitro"],"prefix":"10.1002","volume":"36","author":[{"given":"Laya","family":"Naderbar","sequence":"first","affiliation":[{"name":"Biology department, Faculty of Sciences Urmia University Urmia Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0572-2980","authenticated-orcid":false,"given":"Yaghub","family":"Pazhang","sequence":"additional","affiliation":[{"name":"Biology department, Faculty of Sciences Urmia University Urmia Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jafar","family":"Rezaie","sequence":"additional","affiliation":[{"name":"Solid Tumor Research Center, Cellular and Molecular Medicine Institute Urmia University of Medical Sciences Urmia Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,8,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25792"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0776-2"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00213-8"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-020-0341-y"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.4103\/aam.aam_56_18"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27411"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/are.12118"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.23150"},{"issue":"7","key":"e_1_2_9_10_1","first-page":"1971","volume":"19","author":"Solanki R.","year":"2018","journal-title":"Asian Pacific J. 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