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Forschungsdatenbank PMU-SQQUID

Increased resistance to trail-induced apoptosis in prostate cancer cells selected in the presence of bicalutamide.
Mitterberger, M; Neuwirt, H; Cavarretta, IT; Hobisch, A; Culig, Z;
Prostate. 2007; 67(11):1194-1201
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Mitterberger Michael

Abstract

BACKGROUND. Following prolonged treatment with the non-steroidal anti-androgen bicalutamide (Casodex), LNCaP cells have become resistant to this drug. Previously, we found that the bicalutamide-refractory subline LNCaP-Bic acquires a growth advantage and does not respond to androgenic stimulation. In the present study, we have asked whether changes in response to the tumor-selective apoptosis inducer TNF-related apoptosis-inducing ligand (TRAIL) occur in LNCaP-Bic cells. METHODS. LNCaP and LNCaP-Bic cells were incubated with increasing concentrations of TRAIL and apoptosis rate was analyzed using FACS. Expression of death receptors (DR), adaptor protein Fas-associated death domain (FADD), members of the Bcl-2 family, and caspases were investigated by Western blot. RESULTS. The percentage of cells undergoing apoptosis was lower in LNCaP-Bic in comparison to LNCaP cells. There were no major differences in death receptor expression between control LNCaP and bicalutamide-selected cells. Surprisingly, treatment with TRAIL increased the levels of Bcl-2 by 50% in LNCaP-Bic cells. The ratio cleaved caspase/procaspase-8 was substantially lower in LNCaP-Bic cells. CONCLUSIONS. Reduced sensitivity to TRAIL-induced apoptosis is a novel mechanism relevant to resistance to bicalutamide in prostate cancer. Inability of TRAIL to cause programmed cell death might be caused by multiple perturbations in the TRAIL-signaling pathway. Prostate 67:1194-1201, 2007. (c) 2007 Wiley-Liss, Inc.


Useful keywords (using NLM MeSH Indexing)

Androgen Antagonists/pharmacology*

Anilides/pharmacology*

Antineoplastic Agents/pharmacology

Apoptosis/drug effects*

Caspases/analysis

Cell Line, Tumor

Drug Resistance, Neoplasm

Humans

Male

Nitriles/pharmacology*

Prostatic Neoplasms/chemistry

Prostatic Neoplasms/pathology*

Proto-Oncogene Proteins c-bcl-2/analysis

Receptors, Death Domain/analysis

Receptors, Death Domain/drug effects

TNF-Related Apoptosis-Inducing Ligand/administration*

dosage

TNF-Related Apoptosis-Inducing Ligand/pharmacology*

Tosyl Compounds/pharmacology*

bcl-2-Associated X Protein/analysis


Find related publications in this database (Keywords)

prostate tumor
anti-androgen resistance
cell death
death receptors
caspases