On the basis of recent evidence indicating a plausible link between cholesterol esterification, expression and rate of growth in different models of human proliferative diseases, the aim of this study was to investigate the association of MDR1 and cholesterol esterification with the growth in leukemia cells. Lymphoid leukemic cells isolated from patients with acute or chronic lymphocytic leukemia and CEM cells were treated with two inhibitors of cholesterol esterification: SaH 58-035 and progesterone. Results showed a 60% average reduction of proliferation rate in leukemia cells treated with each cholesterol esterification inhibitor. This effect was not caused by cell toxicity, as cell morphology and viability were unaffected. In addition, it appears that changes in the cholesterol biosynthetic pathway are not responsible for the antiproliferative effect observed, being cholesterol synthesis unaltered. The inhibition of cell proliferation was associated with a reduction of ACAT and MDR1 mRNA expression and conversely with an up-regulation of p-53 protein expression. ACAT inhibitors, by reducing cellular cholesterol esters and MDR1 gene expression and through these pathways the proliferation rate of leukemia cells, may warrant consideration as innovative targeted anticancer agents.

INHIBITION OF CHOLESTEROL ESTERIFICATION IN THE CONTROL OF LEUKEMIA PROLIFERATION IN VITRO

GASPERI CAMPANI, ANNA;BAIOCCHI, DANIELA;RONCUZZI, LAURA;
2008

Abstract

On the basis of recent evidence indicating a plausible link between cholesterol esterification, expression and rate of growth in different models of human proliferative diseases, the aim of this study was to investigate the association of MDR1 and cholesterol esterification with the growth in leukemia cells. Lymphoid leukemic cells isolated from patients with acute or chronic lymphocytic leukemia and CEM cells were treated with two inhibitors of cholesterol esterification: SaH 58-035 and progesterone. Results showed a 60% average reduction of proliferation rate in leukemia cells treated with each cholesterol esterification inhibitor. This effect was not caused by cell toxicity, as cell morphology and viability were unaffected. In addition, it appears that changes in the cholesterol biosynthetic pathway are not responsible for the antiproliferative effect observed, being cholesterol synthesis unaltered. The inhibition of cell proliferation was associated with a reduction of ACAT and MDR1 mRNA expression and conversely with an up-regulation of p-53 protein expression. ACAT inhibitors, by reducing cellular cholesterol esters and MDR1 gene expression and through these pathways the proliferation rate of leukemia cells, may warrant consideration as innovative targeted anticancer agents.
898.39
898.39
Gasperi-Campani A.; Batetta B.; Baiocchi D.; Putzolu M.; Roncuzzi L.; Dessì S.
File in questo prodotto:
Eventuali allegati, non sono esposti

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/70479
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact