Linked Life Data

18949618

Source:http://linkedlifedata.com/resource/pubmed/id/18949618

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2008-10-24
pubmed:abstractText
Involvement of phosphatidylinositol 3-kinase/Akt-1 in cell survival and proliferation of multiple myeloma (MM) has been well established. In this study, we demonstrate that homoharringtonine (HHT), an antileukemic drug first isolated from the Chinese evergreen Cephalotaxus harringtonia, induces significant cytotoxicity in dexamethasone-sensitive and -resistant and chemotherapy-sensitive MM cell lines in a time and dose-dependent manner. HHT also triggers apoptosis in chemotherapy-resistant patient's myeloma cells. Contrary to dexamethasone, the cytotoxicity of HHT on myeloma is independent of interleukin-6. The mechanism of HHT cytotoxicity is related to down-regulation of Akt phosphorylation/activation and various target genes of Akt including nuclear factor kappa B, XIAP, cIAP and cyclin D1. Moreover, in vivo antitumor activity of HHT is demonstrated in RPMI8226 myeloma xenograft model. Importantly, an additive effect of antitumor is confirmed in the myeloma cells treated with HHT and bortezomib concomitantly with inhibition of phosphorylated Akt. Together, these findings obtained with HHT should give useful insights into a novel antimyeloma chemotherapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1029-2403
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1954-62
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Homoharringtonine inhibits the AKT pathway and induces in vitro and in vivo cytotoxicity in human multiple myeloma cells.
pubmed:affiliation
Institute of Hematology, the First Affiliated Hospital, Zhejiang University, Key lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, People's Republic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't