Document Detail

Carboxyamido-triazole (CAI), a signal transduction inhibitor induces growth inhibition and apoptosis in bladder cancer cells by modulation of Bcl-2.
MedLine Citation:
PMID:  15517890     Owner:  NLM     Status:  MEDLINE    
Pro- and anti-apoptotic factors and intracellular signaling pathways are targets for therapeutic development of anticancer agents. Carboxyamido-triazole (CAI) is an inhibitor of transmembrane calcium influx and intracellular calcium-requiring signal transduction pathways. The present study investigates the effects of CAI on human transitional cancer cell (TCC) viability and apoptosis, and evaluates whether apoptotic resistance may be overcome pharmacologically. Both well-differentiated (RT4, RT112/grade 1) and poorly-differentiated (T24/grade 3; SUP/grade 4) human TCC lines were shown to express Fas. Upon exposure to agonistic monoclonal Fas antibody, only well-differentiated TCC lines underwent apoptotic cell death. CAI exposure reduced cell viability and caused an at least additive anti-apoptotic effect in combination with the Fas antibody in the Fas-insensitive TCC lines. Under the same conditions under which CAI treatment augmented Fas-mediated apoptosis, it was shown to reduce intracellular bcl-2 quantity. This response to CAI indicates that apoptotic cell death is enhanced by the reduction of bcl-2 protein expression. We suggest that the antitumor effect of CAI is at least partially based on restoring a pathway of apoptosis. It may cause transformation of cell homeostasis that leads to the alteration of apoptotic mechanisms, thus allowing highly malignant tumor cells to re-enter the physiological course of cell elimination.
Frank G E Perabo; Andreas Wirger; Stefan Kamp; Heike Lindner; Doris H Schmidt; Stefan C Müller; Elise C Kohn
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anticancer research     Volume:  24     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:    2004 Sep-Oct
Date Detail:
Created Date:  2004-11-02     Completed Date:  2004-12-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  2869-77     Citation Subset:  IM    
Department of Urology, University Hospital, Bonn University, 53105 Bonn, USA.
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MeSH Terms
Antibodies, Monoclonal / immunology,  pharmacology
Antigens, CD95 / biosynthesis,  immunology
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Calcium / metabolism
Carcinoma, Transitional Cell / drug therapy*,  metabolism,  pathology
Cell Growth Processes / drug effects
Cell Line, Tumor
Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
Signal Transduction / drug effects
Triazoles / pharmacology*
Urinary Bladder Neoplasms / drug therapy*,  metabolism,  pathology
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD95; 0/Antineoplastic Agents; 0/Proto-Oncogene Proteins c-bcl-2; 0/Triazoles; 7440-70-2/Calcium; 99519-84-3/carboxyamido-triazole

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