UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

s-thalidomide has a greater effect on apoptosis than angiogenesis in a multiple myeloma cell line

Liu, WM; Strauss, SJ; Chaplin, T; Shahin, S; Propper, DJ; Young, BD; Joel, SP; (2004) s-thalidomide has a greater effect on apoptosis than angiogenesis in a multiple myeloma cell line. Hematol J , 5 (3) 247-54-247-54.

Full text not available from this repository.

Abstract

s-Thalidomide has proven efficacy in multiple myeloma. Although it has both antiangiogenic and pro-apoptotic effects, its primary mode of therapeutic action remains unclear. We have investigated the changes to the expression of genes involved with these cellular processes following culture with s-thalidomide in the U266 MM cell line. Cells were cultured with s-thalidomide (0-1000 microM), and cell parameters, including apoptosis, were assessed on day 3. RNA was extracted from cells cultured for 24 h at the IC(50) concentration of s-thalidomide, and changes to gene expression were investigated by microarray methodologies. A reduction in cell viability was observed in U266 cells cultured with s-thalidomide (IC(50): 362 microM), which were mirrored by significant increases in apoptosis (for example, 200 microM on day 3: 40.3+/-3.1% vs. 3.2+/-0.4% on day 0; P<0.001). There were changes in the expression profile of genes involved in angiogenesis and apoptosis, but the changes were most dramatic in the apoptotic genes. In particular, the expression of I-kappaB kinase was decreased by two-fold, which was associated with a four-fold decrease in NF-kappaB expression. These data correlated with immunoblotting analyses, which showed significant increases in I-kappaB protein levels and decreased NF-kappaB activity. Additionally, the Bax : Bcl-2 ratio was significantly increased. Our data suggest that both angiogenic and apoptotic genes and proteins are affected by s-thalidomide. Additionally, a dramatic decrease in Bcl-2 expression with s-thalidomide suggests a possible enhancement of cytotoxic effect if combined with other cytotoxic agents.

Type: Article
Title: s-thalidomide has a greater effect on apoptosis than angiogenesis in a multiple myeloma cell line
Additional information: uri: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15167912
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: http://discovery.ucl.ac.uk/id/eprint/1305854
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item