Bortezomib Sensitizes Human Esophageal Squamous Cell Carcinoma Cells to TRAIL-Mediated Apoptosis

Strategic Insights -

Scientists in Kurume, Japan, have investigated the therapeutic potential of the combination of the proteasome inhibitor bortezomib and the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) on human esophageal squamous cell carcinoma (ESCC) cell lines. The study found that bortezomib enhanced the susceptibility of ESCC cells to TRAIL-induced apoptosis, and that this effect was mediated by both extrinsic and intrinsic apoptosis pathways. The researchers concluded that the combination of bortezomib and TRAIL might be a novel therapeutic strategy for ESCC patients who fail to respond to standard chemoradiotherapy.

Key Takeaways:

  • Bortezomib sensitized 12 out of 15 ESCC cell lines tested to TRAIL-mediated apoptosis.
  • The enhancement of TRAIL-induced apoptosis by bortezomib was caspase dependent and involved the increased processing of caspase-8.
  • Bortezomib treatment resulted in a more efficient recruitment of caspase-8 and the Fas-associated death domain to the death-inducing signaling complex.
  • The cellular FLICE-inhibitory protein long isoform (c-FLIP(L)) was downregulated in some ESCC cell lines after bortezomib treatment.
  • Bortezomib could sensitize ESCC to TRAIL apoptosis by multiple molecular mechanisms of action.
  • The combination of bortezomib and TRAIL might be a novel therapeutic strategy for ESCC patients who fail to respond to standard chemoradiotherapy.
  • The study was conducted by N. Seki and colleagues at the Research Center for Innovative Cancer Therapy, Kurume University.

Statistics:

  • 12 out of 15 ESCC cell lines tested were sensitized to TRAIL-mediated apoptosis by bortezomib.
  • The enhancement of TRAIL-induced apoptosis by bortezomib was caspase dependent in 12 out of 15 ESCC cell lines tested.
  • 8 out of 15 ESCC cell lines tested showed increased signaling via the intrinsic apoptotic pathway after bortezomib treatment.

Sources:

  • Seki, N., et al. (2010). Bortezomib sensitizes human esophageal squamous cell carcinoma cells to TRAIL-mediated apoptosis via activation of both extrinsic and intrinsic apoptosis pathways. Molecular Cancer Therapeutics, 9(6), 1842-1851.
  • This article was prepared by Biotech Week editors from staff and other reports. Copyright 2010, Biotech Week via NewsRx.com.