{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T16:49:13Z","timestamp":1789750153066,"version":"4.0.1"},"reference-count":51,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T00:00:00Z","timestamp":1681344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Polpharma Scientific Foundation","award":["1027.0641.33.2020"],"award-info":[{"award-number":["1027.0641.33.2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acute myeloid leukemia (AML) is a hematological malignancy characterized by excessive proliferation of abnormal myeloid precursors accompanied by a differentiation block and inhibition of apoptosis. Increased expression of an anti-apoptotic MCL-1 protein was shown to be critical for the sustained survival and expansion of AML cells. Therefore, herein, we examined the pro-apoptotic and pro-differentiating effects of S63845, a specific inhibitor of MCL-1, in a single-agent treatment and in combination with BCL-2\/BCL-XL inhibitor, ABT-737, in two AML cell lines: HL-60 and ML-1. Additionally, we determined whether inhibition of the MAPK pathway had an impact on the sensitivity of AML cells to S63845. To assess AML cells\u2019 apoptosis and differentiation, in vitro studies were performed using PrestoBlue assay, Coulter electrical impedance method, flow cytometry, light microscopy and Western blot techniques. S63845 caused a concentration-dependent decrease in the viability of HL-60 and ML-1 cells and increased the percentage of apoptotic cells. Combined treatment with S63845 and ABT-737 or MAPK pathway inhibitor enhanced apoptosis but also induced differentiation of tested cells, as well as altering the expression of the MCL-1 protein. Taken together, our data provide the rationale for further studies regarding the use of MCL-1 inhibitor in combination with other pro-survival protein inhibitors.<\/jats:p>","DOI":"10.3390\/ijms24087180","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T02:29:15Z","timestamp":1681352955000},"page":"7180","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Synergistic Action of MCL-1 Inhibitor with BCL-2\/BCL-XL or MAPK Pathway Inhibitors Enhances Acute Myeloid Leukemia Cell Apoptosis and Differentiation"],"prefix":"10.3390","volume":"24","author":[{"given":"Ma\u0142gorzata","family":"Opydo","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Hematology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Mlyczy\u0144ska","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Hematology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7471-0553","authenticated-orcid":false,"given":"Ewa","family":"Mlyczy\u0144ska","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, 30-387 Krakow, Poland"},{"name":"Doctoral School of Exact and Natural Sciences, Jagiellonian University, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9572-7151","authenticated-orcid":false,"given":"Agnieszka","family":"Rak","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3573-3584","authenticated-orcid":false,"given":"Elzbieta","family":"Kolaczkowska","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Hematology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4798","DOI":"10.1038\/sj.onc.1209608","article-title":"Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy","volume":"25","author":"Fulda","year":"2006","journal-title":"Oncogene"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.tcb.2013.07.006","article-title":"Evading apoptosis in cancer","volume":"23","author":"Fernald","year":"2013","journal-title":"Trends Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"112446","DOI":"10.1016\/j.ejmech.2020.112446","article-title":"Single and dual target inhibitors based on Bcl-2: Promising anti-tumor agents for cancer therapy","volume":"201","author":"Liu","year":"2020","journal-title":"Eur. 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