{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T07:08:19Z","timestamp":1790060899429,"version":"4.0.1"},"reference-count":32,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T00:00:00Z","timestamp":1591920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>\u03b2-adrenergic signaling is known to be involved in cancer progression; in particular, beta3-adrenoreceptor (\u03b23-AR) is associated with different tumor conditions. Currently, there are few data concerning \u03b23-AR in myeloid malignancies. Here, we evaluated \u03b23-AR in myeloid leukemia cell lines and the effect of \u03b23-AR antagonist SR59230A. In addition, we investigated the potential role of \u03b23-AR blockade in doxorubicin resistance. Using flow cytometry, we assessed cell death in different in vitro myeloid leukemia cell lines (K562, KCL22, HEL, HL60) treated with SR59230A in hypoxia and normoxia; furthermore, we analyzed \u03b23-AR expression. We used healthy bone marrow cells (BMCs), peripheral blood mononuclear cells (PBMCs) and cord blood as control samples. Finally, we evaluated the effect of SR59230A plus doxorubicin on K562 and K562\/DOX cell lines; K562\/DOX cells are resistant to doxorubicin and show P-glycoprotein (P-gp) overexpression. We found that SR59230A increased cancer cell lines apoptosis especially in hypoxia, resulting in selective activity for cancer cells; moreover, \u03b23-AR expression was higher in malignancies, particularly under hypoxic condition. Finally, we observed that SR59230A plus doxorubicin increased doxorubicin resistance reversion mainly in hypoxia, probably acting on P-gp. Together, these data point to \u03b23-AR as a new target and \u03b23-AR blockade as a potential approach in myeloid leukemias.<\/jats:p>","DOI":"10.3390\/ijms21124210","type":"journal-article","created":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T03:17:32Z","timestamp":1592191052000},"page":"4210","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["\u03b23-Adrenoreceptor Blockade Reduces Hypoxic Myeloid Leukemic Cells Survival and Chemoresistance"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0750-4706","authenticated-orcid":false,"given":"Maura","family":"Calvani","sequence":"first","affiliation":[{"name":"Division of Pediatric Oncology\/Hematology, Meyer University Children\u2019s Hospital, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Dabraio","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology\/Hematology, Meyer University Children\u2019s Hospital, 50139 Florence, Italy"},{"name":"Department of Health Sciences, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6252-3825","authenticated-orcid":false,"given":"Gennaro","family":"Bruno","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology\/Hematology, Meyer University Children\u2019s Hospital, 50139 Florence, Italy"},{"name":"Department of Health Sciences, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"De Gregorio","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology\/Hematology, Meyer University Children\u2019s Hospital, 50139 Florence, Italy"},{"name":"Department of Health Sciences, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"Coronnello","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Costanza","family":"Bogani","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Ciullini","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology\/Hematology, Meyer University Children\u2019s Hospital, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo la","family":"Marca","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7715-8207","authenticated-orcid":false,"given":"Marina","family":"Vignoli","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology\/Hematology, Meyer University Children\u2019s Hospital, 50139 Florence, Italy"},{"name":"Department of Health Sciences, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Chiarugi","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Nardi","sequence":"additional","affiliation":[{"name":"Onco-Hematologic Pediatric Center, University Hospital of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro Maria","family":"Vannucchi","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5310-9147","authenticated-orcid":false,"given":"Luca","family":"Filippi","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, Medical Surgical Fetal-Neonatal Department, Meyer University Children\u2019s Hospital, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Favre","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology\/Hematology, Meyer University Children\u2019s Hospital, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.2147\/JBM.S221317","article-title":"Myeloid Leukemias: A Glance at Middle Eastern Centers","volume":"10","author":"Khaled","year":"2019","journal-title":"J. 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