Journal
CANCER GENE THERAPY
Volume 9, Issue 2, Pages 164-172Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.cgt.7700420
Keywords
TRAIL/Apo2L; doxorubicin; adenovirus; apoptosis; prostate; cancer
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Funding
- NCI NIH HHS [R01 CA69596] Funding Source: Medline
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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) ha been shown to induce apoptosis in malignant cells without harming normal cells. To determine the antitumor potential of TRAIL against prostate cells, we undertook a comprehensive study that included eight prostate cancer cells lines (CWR22Rv1, Du145, Dupre, JCA-1, LNCaP, PC-3, PPC-1, and TsuPr1) and primary Cultures of normal prostate epithelial cells (PrEC). Cells were tested for susceptibility to soluble TRAIL in the presence or absence of the chemotherapeutic agent doxorubicin. TRAIL was also delivered by an adenoviral vector. Our results reveal that Du145, DuPro, LNCap, TsuPr1, and PrEC were resistant to 100 ng/mL TRAIL. JCA-1 and PPC-1 were slightly sensitive (20% killing) and PC-3 and CWR22Rv1 exhibited the highest sensitivity to TRAIL (30% and 50% killing, respectively). The combination of 10 ng/mL TRAIL with doxorubicin resulted in 60-80% cytotoxicity in seven of eight prostate cancer cells. TRAIL-mediated apoptosis involved cleavage of Bid, caspase-3, and PARP, and required caspase-8 and -9 activity. Full-length TRAIL delivered by an adenoviral vector (AdTRAIL-IRES-GFP) killed prostate cancer cell lines and PrEC without requisite doxorubicin cotreatment. Therefore, expression of the transgene from a tissue-specific promotor would make gene therapy with AdTRAIL-IRES-GFP a possibility.
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