Edelfosine and Miltefosine Effects on Lipid Raft Properties: Membrane Biophysics in Cell Death by Antitumor Lipids

2013 ◽  
Vol 117 (26) ◽  
pp. 7929-7940 ◽  
Author(s):  
Bruno M. Castro ◽  
Aleksander Fedorov ◽  
Valentin Hornillos ◽  
Javier Delgado ◽  
A Ulises Acuña ◽  
...  
Keyword(s):  
Cell Death ◽  
Lipid Raft ◽  
Membrane Biophysics

scholarly journals The dependence receptor DCC requires lipid raft localization for cell death signaling

2006 ◽  
Vol 103 (11) ◽  
pp. 4128-4133 ◽  
Author(s):  
C. Furne ◽  
V. Corset ◽  
Z. Herincs ◽  
N. Cahuzac ◽  
A.-O. Hueber ◽  
...  
Keyword(s):  
Cell Death ◽  
Lipid Raft ◽  
Cell Death Signaling ◽  
Dependence Receptor

scholarly journals Vibrio vulnificus VvhA induces autophagy-related cell death through the lipid raft-dependent c-Src/NOX signaling pathway

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Eun Ju Song ◽  
Sei-Jung Lee ◽  
Hyeon Su Lim ◽  
Jun Sung Kim ◽  
Kyung Ku Jang ◽  
...  
Keyword(s):  
Cell Death ◽  
Signaling Pathway ◽  
Lipid Raft ◽  
Vibrio Vulnificus ◽  
Related Cell

scholarly journals Phospholipase D promotes Arcanobacterium haemolyticum adhesion via lipid raft remodeling and host cell death following bacterial invasion

2010 ◽  
Vol 10 (1) ◽  
pp. 270 ◽  
Author(s):  
Erynn A Lucas ◽  
Stephen J Billington ◽  
Petteri Carlson ◽  
David J McGee ◽  
B Helen Jost
Keyword(s):  
Cell Death ◽  
Host Cell ◽  
Phospholipase D ◽  
Lipid Raft ◽  
Bacterial Invasion ◽  
Host Cell Death ◽  
Arcanobacterium Haemolyticum

scholarly journals Alemtuzumab induces caspase-independent cell death in human chronic lymphocytic leukemia cells through a lipid raft-dependent mechanism

Leukemia ◽  
2005 ◽  
Vol 20 (2) ◽  
pp. 272-279 ◽  
Author(s):  
A P Mone ◽  
C Cheney ◽  
A L Banks ◽  
S Tridandapani ◽  
N Mehter ◽  
...  
Keyword(s):  
Cell Death ◽  
Chronic Lymphocytic Leukemia ◽  
Lipid Raft ◽  
Lymphocytic Leukemia ◽  
Leukemia Cells ◽  
Dependent Mechanism

Lipid raft localization and palmitoylation: Identification of two requirements for cell death induction by the tumor suppressors UNC5H

2008 ◽  
Vol 314 (14) ◽  
pp. 2544-2552 ◽  
Author(s):  
Carine Maisse ◽  
Aurélie Rossin ◽  
Nathalie Cahuzac ◽  
Andrea Paradisi ◽  
Catherine Klein ◽  
...  
Keyword(s):  
Cell Death ◽  
Lipid Raft ◽  
Tumor Suppressors

Green tea polyphenol EGCG induces lipid-raft clustering and apoptotic cell death by activating protein kinase Cδ and acid sphingomyelinase through a 67 kDa laminin receptor in multiple myeloma cells

2012 ◽  
Vol 443 (2) ◽  
pp. 525-534 ◽  
Author(s):  
Shuntaro Tsukamoto ◽  
Keisuke Hirotsu ◽  
Motofumi Kumazoe ◽  
Yoko Goto ◽  
Kaori Sugihara ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Death ◽  
Protein Kinase ◽  
Lipid Raft ◽  
Apoptotic Cell ◽  
Acid Sphingomyelinase ◽  
Laminin Receptor ◽  
Myeloma Cells ◽  
Raft Clustering ◽  
Protein Kinase Cδ

EGCG [(−)-epigallocatechin-3-O-gallate], the major polyphenol of green tea, has cancer chemopreventive and chemotherapeutic activities. EGCG selectively inhibits cell growth and induces apoptosis in cancer cells without adversely affecting normal cells; however, the underlying molecular mechanism in vivo is unclear. In the present study, we show that EGCG-induced apoptotic activity is attributed to a lipid-raft clustering mediated through 67LR (67 kDa laminin receptor) that is significantly elevated in MM (multiple myeloma) cells relative to normal peripheral blood mononuclear cells, and that aSMase (acid sphingomyelinase) is critical for the lipid-raft clustering and the apoptotic cell death induced by EGCG. We also found that EGCG induces aSMase translocation to the plasma membrane and PKCδ (protein kinase Cδ) phosphorylation at Ser664, which was necessary for aSMase/ceramide signalling via 67LR. Additionally, orally administered EGCG activated PKCδ and aSMase in a murine MM xenograft model. These results elucidate a novel cell-death pathway triggered by EGCG for the specific killing of MM cells.

Alemtuzumab Induces Cell Death in Human Chronic Lymphocytic Leukemia Cells through a Lipid Raft-Dependent Mechanism.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2507-2507
Author(s):  
Andrew P. Mone ◽  
Carolyn Cheney ◽  
Amy Banks ◽  
Sara Jefferson ◽  
Thomas Lin ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Mtt Assay ◽  
Lipid Raft ◽  
Cytochalasin B ◽  
Annexin V ◽  
Immunoblot Analysis ◽  
Parp Cleavage ◽  
Cross Linking ◽  
Effector Cells

Abstract Campath-1H is a humanized IgG1 kappa antibody directed against the cell surface antigen CD52, a GPI linked protein of unknown function that is present on B and T lymphocytes as well as CLL cells. Campath-1H is approved for fludarabine refractory CLL and ongoing studies will continue to define its role in the treatment of CLL. Despite its clinical use, little is known about the in vivo mechanism of its cytotoxicity. Mechanisms invoking complement, effector cells and direct antibody- induced cytotoxicity have been proposed. Here we show that campath-1H is directly toxic to human CLL cells in vitro in the absence of complement or effector cells. Furthermore, we observed that normal T-cells isolated from random blood donors are less sensitive to direct campath-1H induced cytotoxicity than CLL cells. Using annexin V-FITC/propidium iodide (PI) staining with FACS analysis, we found that treatment of CLL samples for 4 hrs with campath-1H (10μg/ml) or campath-1H with a cross-linking anti-Fc IgG (10μg/ml) leads to positive staining in 9.5 % and 29% of the cell respectively (n=11). Parallel study using the MTT assay showed a 7.9 % and 20.4 % loss of viability with campath-1H or campath-1H + anti-Fc IgG (n=5). Antibody directed cellular cytoxicity, using the chromium release assay, showed 20 % killing at 4 hrs (effector to target cell ratio 25:1, n = 4). After treating primary CLL cells with campath-1H for 4 hrs in the presence of human complement, 67 % of the cells stained positive with annexin V-FITC/PI (n=5). Direct campath-1H induced killing of normal T-cells was reduced compared to CLL cells. After a 4 hr treatment with campath-1H + anti-Fc IgG, 6.7 % of the cells stained positive with annexin V-FITC/PI (n=5). The direct campath-1H cytoxicity we observed in CLL cells is caspase-independent. Immunoblot analysis showed no evidence of caspase-3, 8, or 9 activation or PARP cleavage, nor was there a reduction in cytotoxicity with the addition of Z-VAD-fmk. Using minimal detergent solubilization of CLL cells followed by density-gradient centrifugation and immunoblot analysis, we found that CD52 colocalizes with the glycosphingolipid GM1. Fluorescence microscopy analysis revealed that upon cross-linking CD52 with campath-1H + anti-Fc IgG, large patches, and in many cases caps, enriched in CD52 and GM1 formed on the plasma membrane of primary CLL cells. Cholesterol depletion of lymphocyte membranes with methyl-β-cyclodextran diminished the formation of these CD52 and GM1 enriched patches and caps. Inhibition of actin polymerization with cytochalasin B also reduced the formation of campath-1H + anti-Fc IgG induced caps. The cytotoxic effect of cross-linked campath-1H upon CLL cells was reduced by methyl-β-cyclodextran or cytochalasin B pretreatment as measured by annexin V-FITC/PI staining and MTT assay analysis. In conclusion, we found that campath-1H treatment of CLL cells leads to rapid cell death through a caspase-independent mechanism in the absence of complement or effector cells. Experiments using methyl-β-cyclodextran or cytochalasin B treated cells, suggest that the direct cytotoxicity of campath-1H is dependent on formation of large antigen/lipid raft aggregates upon the cell membrane, with underlying cytoskeletal rearrangement. The difference in direct killing observed between CLL cells and normal T-cells suggests that death mechanisms may differ significantly and thus provide the opportunity to refine CD52 directed antibodies with the aim of reducing the suppression of cellular immunity.

Sign in / Sign up

Export Citation Format

Share Document