Loss of XIAP protein expression by RNAi and antisense approaches sensitizes cancer cells to functionally diverse chemotherapeutics View Full Text


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Article Info

DATE

2004-09-20

AUTHORS

Dan C McManus, Charles A Lefebvre, Gabriele Cherton-Horvat, Martine St-Jean, Ekambar R Kandimalla, Sudhir Agrawal, Stephen J Morris, Jon P Durkin, Eric C LaCasse

ABSTRACT

Stable expression of short-hairpin RNAs (shRNAs) directed against the X-linked inhibitor of apoptosis (XIAP) resulted in the generation of three MDA-MB-231 cell lines (XIAP shRNA cells) with reductions in XIAP mRNA and protein levels >85% relative to MDA-MB-231 cells stably transfected with the U6 RNA polymerase III promoter alone (U6 cells). This RNA interference (RNAi) approach dramatically sensitized these cells to killing by the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Importantly, loss of XIAP also sensitized the cells to killing by taxanes but had no additional effects on killing by carboplatin and doxorubicin. The increased sensitivity of the XIAP shRNA cells to killing by TRAIL and taxanes correlated with enhanced caspase cleavage and activation, including caspase-8, and robust processing of poly(ADP-ribose) polymerase and BID compared to U6 cells. Additionally, increasing XIAP levels by adenovirus-mediated expression protected both XIAP shRNA and U6 cells from TRAIL killing in a dose-dependent manner. The effects observed by stable RNAi with respect to TRAIL sensitization were also achieved following downregulation of XIAP in Panc-1 cells treated with a second-generation, mixed-backbone antisense oligonucleotide, AEG 35156/GEM640. These data indicate that reducing XIAP protein expression by either RNAi or antisense approaches increases cancer cell susceptibility to functionally diverse chemotherapeutic agents and supports the notion that downregulation of XIAP in vivo may synergize with disease-relevant chemotherapeutic regimes, including TRAIL and taxanes, to increase the effectiveness of antineoplastic agents. More... »

PAGES

8105-8117

References to SciGraph publications

  • 2001-01-10. Identification of XAF1 as an antagonist of XIAP anti-Caspase activity in NATURE CELL BIOLOGY
  • 1997-07. X-linked IAP is a direct inhibitor of cell-death proteases in NATURE
  • 1997-08. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma in NATURE MEDICINE
  • 2002-09-01. The Bcl2 family: regulators of the cellular life-or-death switch in NATURE REVIEWS CANCER
  • 2003-11-24. The inhibitors of apoptosis: there is more to life than Bcl2 in ONCOGENE
  • 1997. Life and death decisions: the role of the IAPs in modulating programmed cell death in APOPTOSIS
  • 2003-04-17. Paclitaxel-induced apoptosis in BJAB cells proceeds via a death receptor-independent, caspases-3/-8-driven mitochondrial amplification loop in ONCOGENE
  • 1998-12-24. The inhibitors of apoptosis (IAPs) and their emerging role in cancer in ONCOGENE
  • 2002-01-21. The serine protease Omi/HtrA2 is released from mitochondria during apoptosis. Omi interacts with caspase-inhibitor XIAP and induces enhanced caspase activity in CELL DEATH & DIFFERENTIATION
  • 1999-04-09. Expression and biological activity of X-linked inhibitor of apoptosis (XIAP) in human malignant glioma in CELL DEATH & DIFFERENTIATION
  • 2003-02-12. The X-linked inhibitor of apoptosis protein inhibits taxol-induced apoptosis in LNCaP cells in UROLITHIASIS
  • 2002-02-11. Cloning and characterization of the rat homologues of the Inhibitor of Apoptosis protein 1, 2, and 3 genes. in BMC GENOMICS
  • 2001-07. XIAP, the guardian angel in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2003-06-08. Induction of an interferon response by RNAi vectors in mammalian cells in NATURE GENETICS
  • 2003-08-24. Activation of the interferon system by short-interfering RNAs in NATURE CELL BIOLOGY
  • 2003-06. Killing the messenger: short RNAs that silence gene expression in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/sj.onc.1207967

    DOI

    http://dx.doi.org/10.1038/sj.onc.1207967

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1034770630

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/15378029


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