Targeting the leukemia cell metabolism by the CPT1a inhibition: functional preclinical effects in leukemias.

Abstract

Cancer cells are characterized by perturbations of their metabolic processes. Recent observations demonstrated that the fatty acid oxidation (FAO) pathway may represent an alternative carbon source for anabolic processes in different tumors, therefore appearing particularly promising for therapeutic purposes. Because the carnitine palmitoyl transferase 1a (CPT1a) is a protein that catalyzes the rate-limiting step of FAO, here we investigated the in vitro antileukemic activity of the novel CPT1a inhibitor ST1326 on leukemia cell lines and primary cells obtained from patients with hematologic malignancies. By real-time metabolic analysis, we documented that ST1326 inhibited FAO in leukemia cell lines associated with a dose- and time-dependent cell growth arrest, mitochondrial damage, and apoptosis induction. Data obtained on primary hematopoietic malignant cells confirmed the FAO inhibition and cytotoxic activity of ST1326, particularly on acute myeloid leukemia cells. These data suggest that leukemia treatment may be carried out by targeting metabolic processes.

• Authors: Maria Rosaria Ricciardi, Simone Mirabilii, Matteo Allegretti, Roberto Licchetta, Anna Calarco, Maria Rosaria Torrisi, Robin Foà, Raffaella Nicolai, Gianfranco Peluso, Agostino Tafuri
• Journal: Blood (Blood) Vol. 126 Issue 16 Pg. 1925-9 (Oct 15 2015) ISSN: 1528-0020 [Electronic] United States
• PMID: 26276667 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by The American Society of Hematology.

Chemical References

• Fatty Acids
• Neoplasm Proteins
• ST1326
• CPT1A protein, human
• Carnitine O-Palmitoyltransferase
• Carnitine

Topics

• Carnitine (analogs & derivatives, pharmacology)
• Carnitine O-Palmitoyltransferase (antagonists & inhibitors, metabolism)
• Cell Line, Tumor
• Drug Delivery Systems
• Fatty Acids (metabolism)
• Humans
• Leukemia, Myeloid, Acute (drug therapy, enzymology, pathology)
• Neoplasm Proteins (antagonists & inhibitors, metabolism)
• Oxidation-Reduction (drug effects)