β3-Adrenoreceptor Blockade Reduces Hypoxic Myeloid Leukemic Cells Survival and Chemoresistance
β-adrenergic signaling is known to be involved in cancer progression; in particular, beta3-adrenoreceptor (β3-AR) is associated with different tumor conditions. Currently, there are few data concerning β3-AR in myeloid malignancies. Here, we evaluated β3-AR in myeloid leukemia cell lines and the eff...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/12/4210 |
| _version_ | 1797565419561680896 |
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| author | Maura Calvani Annalisa Dabraio Gennaro Bruno Veronica De Gregorio Marcella Coronnello Costanza Bogani Sara Ciullini Giancarlo la Marca Marina Vignoli Paola Chiarugi Margherita Nardi Alessandro Maria Vannucchi Luca Filippi Claudio Favre |
| author_facet | Maura Calvani Annalisa Dabraio Gennaro Bruno Veronica De Gregorio Marcella Coronnello Costanza Bogani Sara Ciullini Giancarlo la Marca Marina Vignoli Paola Chiarugi Margherita Nardi Alessandro Maria Vannucchi Luca Filippi Claudio Favre |
| author_sort | Maura Calvani |
| collection | DOAJ |
| description | β-adrenergic signaling is known to be involved in cancer progression; in particular, beta3-adrenoreceptor (β3-AR) is associated with different tumor conditions. Currently, there are few data concerning β3-AR in myeloid malignancies. Here, we evaluated β3-AR in myeloid leukemia cell lines and the effect of β3-AR antagonist SR59230A. In addition, we investigated the potential role of β3-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 β3-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, β3-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 β3-AR as a new target and β3-AR blockade as a potential approach in myeloid leukemias. |
| first_indexed | 2024-03-10T19:11:57Z |
| format | Article |
| id | doaj.art-430f896c6b824fc3b876f442650e5366 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T19:11:57Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-430f896c6b824fc3b876f442650e53662023-11-20T03:41:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-06-012112421010.3390/ijms21124210β3-Adrenoreceptor Blockade Reduces Hypoxic Myeloid Leukemic Cells Survival and ChemoresistanceMaura Calvani0Annalisa Dabraio1Gennaro Bruno2Veronica De Gregorio3Marcella Coronnello4Costanza Bogani5Sara Ciullini6Giancarlo la Marca7Marina Vignoli8Paola Chiarugi9Margherita Nardi10Alessandro Maria Vannucchi11Luca Filippi12Claudio Favre13Division of Pediatric Oncology/Hematology, Meyer University Children’s Hospital, 50139 Florence, ItalyDivision of Pediatric Oncology/Hematology, Meyer University Children’s Hospital, 50139 Florence, ItalyDivision of Pediatric Oncology/Hematology, Meyer University Children’s Hospital, 50139 Florence, ItalyDivision of Pediatric Oncology/Hematology, Meyer University Children’s Hospital, 50139 Florence, ItalyDepartment of Health Sciences, University of Florence, 50139 Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, 50139 Florence, ItalyDivision of Pediatric Oncology/Hematology, Meyer University Children’s Hospital, 50139 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, ItalyDivision of Pediatric Oncology/Hematology, Meyer University Children’s Hospital, 50139 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, ItalyOnco-Hematologic Pediatric Center, University Hospital of Pisa, 56126 Pisa, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, 50139 Florence, ItalyNeonatal Intensive Care Unit, Medical Surgical Fetal-Neonatal Department, Meyer University Children’s Hospital, 50139 Florence, ItalyDivision of Pediatric Oncology/Hematology, Meyer University Children’s Hospital, 50139 Florence, Italyβ-adrenergic signaling is known to be involved in cancer progression; in particular, beta3-adrenoreceptor (β3-AR) is associated with different tumor conditions. Currently, there are few data concerning β3-AR in myeloid malignancies. Here, we evaluated β3-AR in myeloid leukemia cell lines and the effect of β3-AR antagonist SR59230A. In addition, we investigated the potential role of β3-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 β3-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, β3-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 β3-AR as a new target and β3-AR blockade as a potential approach in myeloid leukemias.https://www.mdpi.com/1422-0067/21/12/4210chemoresistancemyeloid leukemiaβ3-adrenoreceptor |
| spellingShingle | Maura Calvani Annalisa Dabraio Gennaro Bruno Veronica De Gregorio Marcella Coronnello Costanza Bogani Sara Ciullini Giancarlo la Marca Marina Vignoli Paola Chiarugi Margherita Nardi Alessandro Maria Vannucchi Luca Filippi Claudio Favre β3-Adrenoreceptor Blockade Reduces Hypoxic Myeloid Leukemic Cells Survival and Chemoresistance International Journal of Molecular Sciences chemoresistance myeloid leukemia β3-adrenoreceptor |
| title | β3-Adrenoreceptor Blockade Reduces Hypoxic Myeloid Leukemic Cells Survival and Chemoresistance |
| title_full | β3-Adrenoreceptor Blockade Reduces Hypoxic Myeloid Leukemic Cells Survival and Chemoresistance |
| title_fullStr | β3-Adrenoreceptor Blockade Reduces Hypoxic Myeloid Leukemic Cells Survival and Chemoresistance |
| title_full_unstemmed | β3-Adrenoreceptor Blockade Reduces Hypoxic Myeloid Leukemic Cells Survival and Chemoresistance |
| title_short | β3-Adrenoreceptor Blockade Reduces Hypoxic Myeloid Leukemic Cells Survival and Chemoresistance |
| title_sort | β3 adrenoreceptor blockade reduces hypoxic myeloid leukemic cells survival and chemoresistance |
| topic | chemoresistance myeloid leukemia β3-adrenoreceptor |
| url | https://www.mdpi.com/1422-0067/21/12/4210 |
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