Nitric oxide sensitizes prostate carcinoma cell lines to TRAIL-mediated apoptosis via inactivation of NF-κB and inhibition of Bcl-xL expression View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2004-03-29

AUTHORS

Sara Huerta-Yepez, Mario Vega, Ali Jazirehi, Hermes Garban, Fumiya Hongo, Genhong Cheng, Benjamin Bonavida

ABSTRACT

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to be selective in the induction of apoptosis in cancer cells with minimal toxicity to normal tissues and this prompted its potential therapeutic application in cancer. However, not all cancers are sensitive to TRAIL-mediated apoptosis and, therefore, TRAIL-resistant cancer cells must be sensitized first to become sensitive to TRAIL. Treatment of prostate cancer (CaP) cell lines (DU145, PC-3, CL-1, and LNCaP) with nitric oxide donors (e.g. (Z)-1-[2-(2-aminoethyl)-N-(2-ammonio-ethyl)amino]diazen-1-ium-1, 2-diolate (DETANONOate)) sensitized CaP cells to TRAIL-induced apoptosis and synergy was achieved. The mechanism by which DETANONOate mediated the sensitization was examined. DETANONOate inhibited the constitutive NF-κB activity as assessed by EMSA. Also, p50 was S-nitrosylated by DETANONOate resulting in inhibition of NF-κB. Inhibition of NF-κB activity by the chemical inhibitor Bay 11-7085, like DETANONOate, sensitized CaP to TRAIL apoptosis. In addition, DETANONOate downregulated the expression of Bcl-2 related gene (Bcl-xL) which is under the transcriptional regulation of NF-κB. The regulation of NF-κB and Bcl-xL by DETANONOate was corroborated by the use of Bcl-xL and Bcl-x κB reporter systems. DETANONOate inhibited luciferase activity in the wild type and had no effect on the mutant cells. Inhibition of NF-κB resulted in downregulation of Bcl-xL expression and sensitized CaP to TRAIL-induced apoptosis. The role of Bcl-xL in the regulation of TRAIL apoptosis was corroborated by inhibiting Bcl-xL function by the chemical inhibitor 2-methoxyantimycin A3 and this resulted in sensitization of the cells to TRAIL apoptosis. Signaling by DETANONOate and TRAIL for apoptosis was examined. DETANONOate altered the mitochondria by inducing membrane depolarization and releasing modest amounts of cytochrome c and Smac/DIABLO in the absence of downstream activation of caspases 9 and 3. However, the combination of DETANONOate and TRAIL resulted in activation of the mitochondrial pathway and activation of caspases 9 and 3, and induction of apoptosis. These findings demonstrate that DETANONOate-mediated sensitization of CaP to TRAIL-induced apoptosis is via inhibition of constitutive NF-κB activity and Bcl-xL expression. More... »

PAGES

4993-5003

References to SciGraph publications

  • 2003-05-02. An MMP-2/MMP-9 inhibitor, 5a, enhances apoptosis induced by ligands of the TNF receptor superfamily in cancer cells in CELL DEATH & DIFFERENTIATION
  • 2001-07-12. Blockade of NF-κB activity in human prostate cancer cells is associated with suppression of angiogenesis, invasion, and metastasis in ONCOGENE
  • 2001-08-01. Tumoricidal activity of a novel anti-human DR5 monoclonal antibody without hepatocyte cytotoxicity in NATURE MEDICINE
  • 2001-05-17. Bcl-2 oncoprotein protects the human prostatic carcinoma cell line PC3 from TRAIL-mediated apoptosis in ONCOGENE
  • 2001-03. Death Receptor Ligands, in Particular TRAIL, to Overcome Drug Resistance in CANCER AND METASTASIS REVIEWS
  • 2000-11. Antisense Downregulation of the Apoptosis-related Bcl-2 and Bcl-xL Proteins: A New Approach to Cancer Therapy in MOLECULAR BIOLOGY
  • 2001-03-22. Sodium nitroprusside enhances TRAIL-induced apoptosis via a mitochondria-dependent pathway in human colorectal carcinoma CX-1 cells in ONCOGENE
  • 1999-11-22. Aberrant rel/nfkb genes and activity in human cancer in ONCOGENE
  • 2002-10. TNF-related apoptosis inducing ligand (TRAIL) and its receptors in tumor surveillance and cancer therapy in APOPTOSIS
  • 1999-12-02. Constitutive activation of IκB kinase α and NF-κB in prostate cancer cells is inhibited by ibuprofen in ONCOGENE
  • 2001-06. Human T-cell Leukemia Virus Type I Tax Protein Induces the Expression of Anti-Apoptotic Gene Bcl-xL in Human T-Cells through Nuclear Factor-κB and c-AMP Responsive Element Binding Protein Pathways in VIRUS GENES
  • 2003-03-18. Interferon-α sensitizes human hepatoma cells to TRAIL-induced apoptosis through DR5 upregulation and NF-κB inactivation in ONCOGENE
  • 2001-01-17. Antimycin A mimics a cell-death-inducing Bcl-2 homology domain 3 in NATURE CELL BIOLOGY
  • 2003-07-01. Progressive resistance of BTK-143 osteosarcoma cells to Apo2L/TRAIL-induced apoptosis is mediated by acquisition of DcR2/TRAIL-R4 expression: resensitisation with chemotherapy in BRITISH JOURNAL OF CANCER
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/sj.onc.1207655

    DOI

    http://dx.doi.org/10.1038/sj.onc.1207655

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/15048072


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