Statin and Bisphosphonate Induce Starvation in Fast-Growing Cancer Cell Lines.
Int J Mol Sci
; 18(9)2017 Sep 15.
Article
en En
| MEDLINE
| ID: mdl-28914765
ABSTRACT
Statins and bisphosphonates are increasingly recognized as anti-cancer drugs, especially because of their cholesterol-lowering properties. However, these drugs act differently on various types of cancers. Thus, the aim of this study was to compare the effects of statins and bisphosphonates on the metabolism (NADPâº/NADPH-relation) of highly proliferative tumor cell lines from different origins (PC-3 prostate carcinoma, MDA-MB-231 breast cancer, U-2 OS osteosarcoma) versus cells with a slower proliferation rate like MG-63 osteosarcoma cells. Global gene expression analysis revealed that after 6 days of treatment with pharmacologic doses of the statin simvastatin and of the bisphosphonate ibandronate, simvastatin regulated more than twice as many genes as ibandronate, including many genes associated with cell cycle progression. Upregulation of starvation-markers and a reduction of metabolism and associated NADPH production, an increase in autophagy, and a concomitant downregulation of H3K27 methylation was most significant in the fast-growing cancer cell lines. This study provides possible explanations for clinical observations indicating a higher sensitivity of rapidly proliferating tumors to statins and bisphosphonates.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Inhibidores de Hidroximetilglutaril-CoA Reductasas
/
Difosfonatos
/
Metabolismo Energético
Límite:
Humans
Idioma:
En
Revista:
Int J Mol Sci
Año:
2017
Tipo del documento:
Article
País de afiliación:
Austria