The sustained rate of proliferation of cancer cells requires metabolic adaptation to satisfy the increased energetic demand and the need of biosynthetic precursors. Growing evidences show that tumor cells adopt enhanced rate of glycolysis and divert fluxes from alternative substrates, such as glutamine and fatty acid (FA), to sustain anabolic processes. Targeting the metabolic reprogramming of neoplastic cells may result in an effective novel approach for pharmacological intervention. In order to evaluate in acute leukemias this strategy, we preliminary measured cellular FA uptake differences between normal and leukemia cells, by flow cytometry using a fluorescent fatty acid analog (BODIPY-C12). Thereafter, taking advantage of ST1326 (Sigma Tau), a molecule capable of selectively and reversibly inhibiting Carnitine Palmitoyl-Transferase 1 (CPT1), a protein catalyzing the FA import into the mitochondria, we evaluated the effectiveness of FA oxidation targeting in acute leukemias. The cy
Fatty acid oxidation and metabolic targeting of leukemia cells by the CPT1 inhibitor ST1326 / Mirabilii, Simone; Ricciardi, Maria Rosaria; Allegretti, Matteo; Licchetta, Roberto; M., Vincenzi; G., Peluso; R., Nicolai; Foà, R.; Tafuri, Agostino. - In: HAEMATOLOGICA. - ISSN 0390-6078. - ELETTRONICO. - 98:(2013). (Intervento presentato al convegno 44° Congress of the Italian Society of Hematology tenutosi a Verona, Italy nel October 20–23, 2013).
Fatty acid oxidation and metabolic targeting of leukemia cells by the CPT1 inhibitor ST1326
MIRABILII, SIMONE;RICCIARDI, Maria Rosaria;ALLEGRETTI, MATTEO;LICCHETTA, ROBERTO;R. Foà;TAFURI, Agostino
2013
Abstract
The sustained rate of proliferation of cancer cells requires metabolic adaptation to satisfy the increased energetic demand and the need of biosynthetic precursors. Growing evidences show that tumor cells adopt enhanced rate of glycolysis and divert fluxes from alternative substrates, such as glutamine and fatty acid (FA), to sustain anabolic processes. Targeting the metabolic reprogramming of neoplastic cells may result in an effective novel approach for pharmacological intervention. In order to evaluate in acute leukemias this strategy, we preliminary measured cellular FA uptake differences between normal and leukemia cells, by flow cytometry using a fluorescent fatty acid analog (BODIPY-C12). Thereafter, taking advantage of ST1326 (Sigma Tau), a molecule capable of selectively and reversibly inhibiting Carnitine Palmitoyl-Transferase 1 (CPT1), a protein catalyzing the FA import into the mitochondria, we evaluated the effectiveness of FA oxidation targeting in acute leukemias. The cyI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.