Inhibition of the ubiquitin-proteasome system sensitizes TRAIL-resistant prostate cancer cells by up-regulation of death receptor 5

  • Authors:
    • You-Jin Lee
    • Jae-Won Seol
    • Jae-Kyo Jeong
    • Myung-Hee Moon
    • Sang‑Youel  Park
  • View Affiliations

  • Published online on: August 16, 2011     https://doi.org/10.3892/mmr.2011.558
  • Pages: 1255-1259
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Abstract

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane cytokine and a potent inducer of apoptosis in cancer cells. However, some cancer cells, particularly prostate cancer cells, such as LNCaP cells, were found to be resistant to TRAIL. In the present study, we demonstrate that the proteasome inhibitor ALLN significantly enhanced TRAIL-induced apoptosis by up-regulating TRAIL/Apo2L death receptor 5 expression in LNCaP cells. LNCaP cells were exposed to ALLN for 3 h and treated with recombinant TRAIL protein. ALLN alone induced a 20% cell death after a 3‑h treatment; however, pretreatment with ALLN induced death to more than 80% of cells after 3 h of TRAIL treatment. ALLN also enhanced the cell death of TRAIL-sensitive/resistant prostate cancer and other cancer cell lines. Western blotting results showed that the combination of ALLN and TRAIL increased the levels of activated caspase-8, -3 and DR-5 in LNCaP cells. Furthermore, we observed an increase in DR-5 expression following 3 h of treatment of ALLN alone. Taken together, our findings indicate that ALLN enhances TRAIL-induced apoptosis in LNCaP cells by up-regulating DR-5 expression. Thus, our results suggest that the combination of ALLN and TRAIL is a novel therapeutic strategy in TRAIL-resistant tumors.

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November-December 2011
Volume 4 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Lee Y, Seol J, Jeong J, Moon M and Park SY: Inhibition of the ubiquitin-proteasome system sensitizes TRAIL-resistant prostate cancer cells by up-regulation of death receptor 5. Mol Med Rep 4: 1255-1259, 2011.
APA
Lee, Y., Seol, J., Jeong, J., Moon, M., & Park, S. (2011). Inhibition of the ubiquitin-proteasome system sensitizes TRAIL-resistant prostate cancer cells by up-regulation of death receptor 5. Molecular Medicine Reports, 4, 1255-1259. https://doi.org/10.3892/mmr.2011.558
MLA
Lee, Y., Seol, J., Jeong, J., Moon, M., Park, S."Inhibition of the ubiquitin-proteasome system sensitizes TRAIL-resistant prostate cancer cells by up-regulation of death receptor 5". Molecular Medicine Reports 4.6 (2011): 1255-1259.
Chicago
Lee, Y., Seol, J., Jeong, J., Moon, M., Park, S."Inhibition of the ubiquitin-proteasome system sensitizes TRAIL-resistant prostate cancer cells by up-regulation of death receptor 5". Molecular Medicine Reports 4, no. 6 (2011): 1255-1259. https://doi.org/10.3892/mmr.2011.558