Evaluation of cytotoxic effects induced by bcl-2 and bcl-xL antisense-oligodeoxynucleotides in normal urothelium and transitional cell carcinoma.
We report on cytotoxic effects of bcl-2 and bcl-xL antisense-oligodeoxynucleotides (AS-ODNs) in benign urothelial and transitional cell carcinoma (TCC) cell lines. The benign urothelial cell line (UROtsa) and four TCC cell lines (UM-UC-3, RT 112 , HT 1197 and T 24/83) were incubated with bcl-2 and bcl-xL AS-ODNs and cell mortality rates were assessed. Bcl-2 and bcl-xL AS-ODN treatment resulted in low toxicity in UROtsa cells (6% and 10% cell mortality, respectively). After bcl-2 AS-ODN treatment, cell mortality rates in TCC cell lines were significantly higher than in UROtsa cells (mean values: 33% vs. 6%, respectively). Bcl-2 AS-ODN treatment also caused significantly higher cell death rates in the majority of TCC cell lines when compared to bcl-xL-AS-ODN therapy (mean values: 33% vs. 11%, respectively). In conclusion, bcl-2 AS-ODNs show significantly higher cell mortality in TCC cells, whereas toxic effects on normal urothelium seem to be minor. Our results suggest favourable characteristics for the clinical application of AS-ODN in intravesical chemotherapy of TCC.
Gabriel
Ute
U
Department of Urology, Mannheim Medical Center, University of Heidelberg, 68167 Mannheim, Germany. ute.gabriel@uro.ma.uni-heidelberg.de
Bolenz
Christian
C
Becker
Andreas
A
Schaaf
Axel
A
Steidler
Annette
A
Trojan
Lutz
L
Weiss
Christel
C
Michel
Maurice Stephan
MS
D002295:Carcinoma, Transitional Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016376:Oligonucleotides, Antisense / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*; D019459:Urothelium / Q000187:drug effects / Q000473:pathology*; D051020:bcl-X Protein / Q000235:genetics* / Q000378:metabolism
D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein