Simultaneous Inhibition of Ceramide Hydrolysis and Glycosylation Synergizes to Corrupt Mitochondrial Respiration and Signal Caspase Driven Cell Death in Drug-Resistant Acute Myeloid Leukemia.

P-glycoprotein acute myeloid leukemia ceramide chemotherapy resistance sphingolipids

Journal

Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829

Informations de publication

Date de publication:
21 Mar 2023
Historique:
received: 14 02 2023
revised: 10 03 2023
accepted: 15 03 2023
medline: 30 3 2023
entrez: 29 3 2023
pubmed: 30 3 2023
Statut: epublish

Résumé

Acute myelogenous leukemia (AML), the most prevalent acute and aggressive leukemia diagnosed in adults, often recurs as a difficult-to-treat, chemotherapy-resistant disease. Because chemotherapy resistance is a major obstacle to successful treatment, novel therapeutic intervention is needed. Upregulated ceramide clearance via accelerated hydrolysis and glycosylation has been shown to be an element in chemotherapy-resistant AML, a problem considering the crucial role ceramide plays in eliciting apoptosis. Herein we employed agents that block ceramide clearance to determine if such a "reset" would be of therapeutic benefit. SACLAC was utilized to limit ceramide hydrolysis, and D-

Identifiants

pubmed: 36980769
pii: cancers15061883
doi: 10.3390/cancers15061883
pmc: PMC10046858
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : NIH HHS
ID : P01 CA171983
Pays : United States
Organisme : BLRD VA
ID : I01 BX001792
Pays : United States
Organisme : BLRD VA
ID : IK6 BX004603
Pays : United States
Organisme : BLRD VA
ID : I01 BX006063
Pays : United States
Organisme : NCI NIH HHS
ID : F31 CA271809
Pays : United States

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Auteurs

Kelsey H Fisher-Wellman (KH)

Department of Integrative Physiology and Metabolism, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC 27858, USA.
UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.

Miki Kassai (M)

East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC 27858, USA.
Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.

James T Hagen (JT)

Department of Integrative Physiology and Metabolism, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC 27858, USA.

P Darrell Neufer (PD)

Department of Integrative Physiology and Metabolism, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC 27858, USA.

Mark Kester (M)

Department of Medicine, Hematology/Oncology, University of Virginia School of Medicine, Charlottesville, VA 22903, USA.
University of Virginia Cancer Center, Charlottesville, VA 22908, USA.

Thomas P Loughran (TP)

Department of Medicine, Hematology/Oncology, University of Virginia School of Medicine, Charlottesville, VA 22903, USA.
University of Virginia Cancer Center, Charlottesville, VA 22908, USA.

Charles E Chalfant (CE)

Department of Medicine, Hematology/Oncology, University of Virginia School of Medicine, Charlottesville, VA 22903, USA.
University of Virginia Cancer Center, Charlottesville, VA 22908, USA.
Department of Cell Biology, University of Virginia, Charlottesville, VA 22903, USA.
Research Service, Richmond Veterans Administration Medical Center, Richmond, VA 23298, USA.

David J Feith (DJ)

Department of Medicine, Hematology/Oncology, University of Virginia School of Medicine, Charlottesville, VA 22903, USA.
University of Virginia Cancer Center, Charlottesville, VA 22908, USA.

Su-Fern Tan (SF)

Department of Medicine, Hematology/Oncology, University of Virginia School of Medicine, Charlottesville, VA 22903, USA.

Todd E Fox (TE)

Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA 22904, USA.

Johnson Ung (J)

Department of Medicine, Hematology/Oncology, University of Virginia School of Medicine, Charlottesville, VA 22903, USA.
University of Virginia Cancer Center, Charlottesville, VA 22908, USA.
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.

Gemma Fabrias (G)

Research Unit on Bioactive Molecules (RUBAM), Department of Biological Chemistry, Institute for Advanced Chemistry of Catalonia (IQAC), Spanish Council for Scientific Research (CSIC), Jordi Girona 18-26, 08034 Barcelona, Spain.

Jose' Luis Abad (JL)

Research Unit on Bioactive Molecules (RUBAM), Department of Biological Chemistry, Institute for Advanced Chemistry of Catalonia (IQAC), Spanish Council for Scientific Research (CSIC), Jordi Girona 18-26, 08034 Barcelona, Spain.

Arati Sharma (A)

Penn State Cancer Institute, Hershey, PA 17033, USA.
Department of Pharmacology, Penn State College of Medicine, Hershey, PA 17033, USA.

Upendarrao Golla (U)

Penn State Cancer Institute, Hershey, PA 17033, USA.
Division of Hematology and Oncology, Penn State Cancer Institute, Hershey, PA 17033, USA.

David F Claxton (DF)

Division of Hematology and Oncology, Penn State Cancer Institute, Hershey, PA 17033, USA.

Jeremy J P Shaw (JJP)

University of Virginia Cancer Center, Charlottesville, VA 22908, USA.
Department of Experimental Pathology, University of Virginia School of Medicine, Charlottesville, VA 22904, USA.

Debajit Bhowmick (D)

Flow Cytometry Division, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.

Myles C Cabot (MC)

East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC 27858, USA.
Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.

Classifications MeSH