Zoledronate has an antitumor effect and induces actin rearrangement in dexamethasone-resistant myeloma cells.
Eur J Haematol
; 79(5): 382-91, 2007 Nov.
Article
em En
| MEDLINE
| ID: mdl-17903213
ABSTRACT
New strategies are needed to overcome the resistance of multiple myeloma (MM) to dexamethasone (Dex). Several recent in vitro studies demonstrated the antitumor effect of nitrogen-containing amino-bisphosphonates (N-BPs) in various tumor cell lines. Inhibition of the prenylation of small G proteins is assumed to be one of the principal mechanisms by which N-BPs exert their effects. There have been few reports on N-BP treatment of MM cells that are resistant to Dex. Additionally, it is not known how small G proteins are altered in N-BP-treated MM cells. In this study, we evaluated the effect of the most potent N-BP, zoledronate (ZOL), on a Dex-resistant human MM cell subline (Dex-R) that we established from the well-documented RPMI8226 cell line. ZOL reduced the viability and induced apoptosis of Dex-R cells. Some of the ZOL-treated RPMI8226 cells and ZOL-treated Dex-R cells were elongated; however, elongated cells were not seen among the Dex-treated RPMI8226 cells. Furthermore, we found that portions of the small G proteins, Rho and Rap1A, were unprenylated in the ZOL-treated MM cells. Geranylgeraniol reduced the above-mentioned ZOL-induced effects. These findings suggest that ZOL may be beneficial for the treatment of Dex-resistant MM by suppressing the processing of RhoA and Rap1A.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dexametasona
/
Actinas
/
Apoptose
/
Resistencia a Medicamentos Antineoplásicos
/
Difosfonatos
/
Imidazóis
/
Mieloma Múltiplo
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article