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Human Agonistic Antibody to Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor 2 Induces Cytotoxicity and Apoptosis in Prostate Cancer and Bladder Cancer Cells
- Source :
- Urology. 69:395-401
- Publication Year :
- 2007
- Publisher :
- Elsevier BV, 2007.
-
Abstract
- OBJECTIVES Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a variety of tumor cells through two of its receptors: TRAIL-R1 and TRAIL-R2. In this study, we investigated the susceptibility of human prostate cancer and bladder cancer cells to HGS-ETR2, a human monoclonal agonistic antibody specific for TRAIL-R2. METHODS The cell surface expression of TRAIL-R1 and TRAIL-R2 on prostate cancer and bladder cancer cells was determined using flow cytometry. Cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and caspase activities were measured by a quantitative colorimetric assay. RESULTS HGS-ETR2 effectively induced apoptotic cell death in DU145, PC3, and LNCaP human prostate cancer cells and J82 and T24 human bladder cancer cells. The increased effectiveness of HGS-ETR2 for inducing cell death might have been affected by differences in the cell surface expression of the two TRAIL receptors, in that TRAIL-R2, but not TRAIL-R1, was frequently expressed in the prostate cancer and bladder cancer cells. HGS-ETR2 significantly activated the caspase cascade, including caspase-3, -6, -8, and -9, which were the downstream molecules of the death receptors in prostate cancer cells. Caspase-3, -6, and -9 were also significantly activated with HGS-ETR2-induced apoptosis in the bladder cancer cells. CONCLUSIONS These findings suggest the potential utility of TRAIL-R2 antibody as a novel therapeutic agent against prostate cancer and bladder cancer.
- Subjects :
- Male
Programmed cell death
Pathology
medicine.medical_specialty
Urology
Apoptosis
urologic and male genital diseases
Sensitivity and Specificity
Prostate cancer
DU145
Cancer stem cell
Cell Line, Tumor
LNCaP
medicine
Humans
Receptors, Tumor Necrosis Factor, Type II
Probability
Bladder cancer
business.industry
Prostatic Neoplasms
Cancer
Flow Cytometry
medicine.disease
Receptors, TNF-Related Apoptosis-Inducing Ligand
Urinary Bladder Neoplasms
Caspases
Cancer cell
Cancer research
Apoptosis Regulatory Proteins
business
Subjects
Details
- ISSN :
- 00904295
- Volume :
- 69
- Database :
- OpenAIRE
- Journal :
- Urology
- Accession number :
- edsair.doi.dedup.....b8caeed30e27db3ca2a4f5fc62099a46