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Research Paper

Proteasome inhibitor Bortezomib induces cell-cycle arrest and apoptosis in cell lines derived from Ewing’s sarcoma family of tumors and synergizes with TRAIL

Guangrong Lu, Vasu Punj and Preet M. Chaudhary

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Bortezomib (VELCADE®), formerly known as PS-341, is a novel dipeptide boronic acid proteasome inhibitor with in vitro and in vivo anti-tumor activity. Bortezomib has been approved for the treatment of multiple myeloma and mantle cell lymphoma. In this report, we examined the sensitivity of cell lines derived from Ewing’s sarcoma-family of tumors (ESFT) to Bortezomib. Five ESFT-derived cell lines, TC-71, TC-32, SK-N-MC, A4573, and GRIMES, were highly sensitive to Bortezomib (IC50 = 20 to 50 nM), and underwent cell-cycle arrest and apoptosis following drug treatment. Bortezomib-induced apoptosis was associated with activation of caspase 3, cleavage of PARP and induction of p27 and p21 expression. Moreover, Bortezomib exhibited synergistic activity against the TC-71 and TC-32 cell lines when combined with TRAIL. Our results suggest that Bortezomib might be a useful agent for treatment of ESFT, when used alone or in combination with TRAIL.

Authors

Guangrong Lu

1 Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas TX 75390-8593

Vasu Punj

Department of Medicine and University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Suite 1.19A, Pittsburgh, PA, 15213-1863

Preet M. Chaudhary

Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas TX 75390-8593; and the 2Department of Medicine and University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Suite 1.19A, Pittsburgh, PA, 15213-1863

Purchase article for $19

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