Document Detail


The melanoma specific 9.2.27PE immunotoxin efficiently kills melanoma cells in vitro.
MedLine Citation:
PMID:  19350633     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Malignant melanomas are generally drug resistant and have a very poor prognosis. We have studied the effects of a chemical conjugate of pseudomonas exotoxin A (PE) and the antibody 9.2.27, which recognizes the high molecular weight melanoma associated antigen (HMW-MAA) expressed in most malignant melanomas and melanoma cell lines. We demonstrate that the 9.2.27PE immunotoxin (IT) induces cell death in malignant melanoma cells through protein synthesis inhibition followed by some morphological and biochemical features of apoptosis, like rounding up of cells, chromatin condensation and inactivation of PARP. Unlike previous results with the 425.3PE IT in breast cancer cells, we detected no depolarization of the mitochondrial membrane after 9.2.27PE IT treatment. This is likely due to the lack of strong activation of caspase-8 and caspase-3. The lack of depolarization suggests that cytochrome c, a molecule that triggers activation of caspase-3, was retained within the mitochondria. In addition, the protein level of the antiapoptotic Bcl-2 did not decrease in contrast to other antiapoptotic molecules belonging to the inhibitor of apoptosis and the Bcl-2 family. This suggests that Bcl-2 may play a role in maintaining the mitochondrial membrane integrity in the 9.2.27PE-treated cells. Nevertheless, 9.2.27PE IT efficiently killed malignant melanoma cells that can be ascribed to inhibition of protein synthesis followed by some morphological and biochemical features of apoptosis.
Authors:
Karianne Risberg; Øystein Fodstad; Yvonne Andersson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  125     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-05-04     Completed Date:  2009-05-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  23-33     Citation Subset:  IM    
Affiliation:
Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Rikshospitalet University Hospital, Oslo, Norway.
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MeSH Terms
Descriptor/Qualifier:
ADP Ribose Transferases / pharmacology*
Antigens, Neoplasm / immunology*
Apoptosis / drug effects*
Bacterial Toxins / pharmacology*
Blotting, Western
Caspase 3 / metabolism
Caspase 8 / metabolism
Cell Line, Tumor
Chromatin / metabolism
Cytochromes c / metabolism
Dose-Response Relationship, Drug
Exotoxins / pharmacology*
Flow Cytometry
Humans
Immunotoxins / pharmacology*
Melanoma / enzymology,  pathology*
Membrane Potential, Mitochondrial / drug effects
Mitochondria / drug effects,  metabolism
Poly(ADP-ribose) Polymerases / metabolism
Protein Synthesis Inhibitors / pharmacology
Proto-Oncogene Proteins c-bcl-2 / metabolism
Time Factors
Virulence Factors / pharmacology*
Chemical
Reg. No./Substance:
0/Antigens, Neoplasm; 0/Bacterial Toxins; 0/Chromatin; 0/Exotoxins; 0/HMW-MAA; 0/Immunotoxins; 0/Protein Synthesis Inhibitors; 0/Proto-Oncogene Proteins c-bcl-2; 0/Virulence Factors; 9007-43-6/Cytochromes c; EC 2.4.2.-/ADP Ribose Transferases; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 2.4.2.31/toxA protein, Pseudomonas aeruginosa; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 8

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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