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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2007-10-10
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pubmed:abstractText |
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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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Actins,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/Diphosphonates,
http://linkedlifedata.com/resource/pubmed/chemical/Diterpenes,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/RAP1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/RHOA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/geranylgeraniol,
http://linkedlifedata.com/resource/pubmed/chemical/rap1 GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/rhoA GTP-Binding Protein,
http://linkedlifedata.com/resource/pubmed/chemical/zoledronic acid
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0902-4441
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
79
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
382-91
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pubmed:dateRevised |
2008-7-29
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pubmed:meshHeading |
pubmed-meshheading:17903213-Actins,
pubmed-meshheading:17903213-Antineoplastic Agents,
pubmed-meshheading:17903213-Apoptosis,
pubmed-meshheading:17903213-Blotting, Western,
pubmed-meshheading:17903213-Cell Line, Tumor,
pubmed-meshheading:17903213-Cell Survival,
pubmed-meshheading:17903213-Dexamethasone,
pubmed-meshheading:17903213-Diphosphonates,
pubmed-meshheading:17903213-Diterpenes,
pubmed-meshheading:17903213-Drug Resistance, Neoplasm,
pubmed-meshheading:17903213-Humans,
pubmed-meshheading:17903213-Imidazoles,
pubmed-meshheading:17903213-Multiple Myeloma,
pubmed-meshheading:17903213-Protein Prenylation,
pubmed-meshheading:17903213-rap1 GTP-Binding Proteins,
pubmed-meshheading:17903213-rhoA GTP-Binding Protein
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pubmed:year |
2007
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pubmed:articleTitle |
Zoledronate has an antitumor effect and induces actin rearrangement in dexamethasone-resistant myeloma cells.
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pubmed:affiliation |
Division of Hematology, Department of Clinical Cell Biology, Chiba University Graduate School of Medicine, Inohana, Chuo-ku, Chiba City, Chiba, Japan.
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pubmed:publicationType |
Journal Article
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