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TRAIL (APO-2L) induces apoptosis in human prostate cancer cells that is inhibitable by Bcl-2

Oncogene volume 20, pages 3757–3765 (2001)Cite this article

Abstract

To determine if TRAIL-induced apoptosis in human prostate tumor cells was suppressed by bcl-2, we compared the levels of apoptosis induced by recombinant human TRAIL in pairs of isogenic cell lines that do or do not express bcl-2. Three human prostate tumor cell lines (PC3, DU145 and LNCaP) and their bcl-2-expressing counterparts were tested for their susceptibility to TRAIL. Cells were exposed to TRAIL in the presence of cycloheximide which acted as a sensitizer. Apoptosis was induced rapidly in PC3 and DU145 neo-control transfected cells, whereas induction in LNCaP required 24 h. All three cell line variants expressing bcl-2 were resistant to the apoptotic effects of TRAIL. Caspase 3 and 8 activation was also detected in the neo control cells after treatment with TRAIL, demonstrating the rapid activation of the caspase cascade similar to that seen with other death receptors. Bcl-2 overexpression in these cells blocked activation of these caspases, suggesting that bcl-2 expression of human cancer cells may be a critical factor in the therapeutic efficacy of TRAIL.

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Acknowledgements

This study was supported in part by grants RO1 CA69003, PO1 CA06294 and P30 CA16672 from the National Cancer Institute.

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Authors and Affiliations

  1. Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, 77030, Texas, TX, USA

    Anupama Munshi, Gus Pappas & Raymond E Meyn

  2. Department of Molecular Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, 77030, Texas, TX, USA

    Tsuyoshi Honda & Timothy J McDonnell

  3. Department of Lymphoma and Leukemia, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, 77030, Texas, TX, USA

    Anas Younes & Yang Li

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  1. Anupama Munshi
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Munshi, A., Pappas, G., Honda, T. et al. TRAIL (APO-2L) induces apoptosis in human prostate cancer cells that is inhibitable by Bcl-2. Oncogene 20, 3757–3765 (2001). https://doi.org/10.1038/sj.onc.1204504

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