The results showed a highly significant 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 at the concentrations of inhibitors used. In addition, it appears that changes in the cholesterol biosynthetic pathway are not responsible for the antiproliferative effect observed, being cholesterol synthesis unaffected in leukemia cells with reduced activity of cholesterol esterification. 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 (p53 not shown). Our results imply that cholesterol esters and MDR1 could play a role in the dynamic processes of lipid transport inside the cells. 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;
2007

Abstract

The results showed a highly significant 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 at the concentrations of inhibitors used. In addition, it appears that changes in the cholesterol biosynthetic pathway are not responsible for the antiproliferative effect observed, being cholesterol synthesis unaffected in leukemia cells with reduced activity of cholesterol esterification. 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 (p53 not shown). Our results imply that cholesterol esters and MDR1 could play a role in the dynamic processes of lipid transport inside the cells. 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.
39
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/11585/56408
 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