Cytotoxicity of tumor necrosis factor related apoptosis-inducing ligand towards Ewing's sarcoma cell lines

Death ligands of the Tumor Necrosis Factor (TNF) family are known to induce apoptosis upon binding to their cognate receptors. However, the clinical utility of these cytokines as anticancer agents has been limited due to unacceptable toxicity. TRAIL is a recently isolated death ligand that possesses selective anti-tumor activity against a number of cancer cell lines without significant systemic toxicity. In this report we present evidence that cell lines derived from Ewing's Sarcoma (ES) are uniformly sensitive to TRAIL-mediated apoptosis. Furthermore, unlike TNF-alpha, treatment with TRAIL fails to induce the anti-apoptotic and pro-inflammatory NF-kappaB pathway in the ES cell lines. Our results suggest that TRAIL may prove to be a useful agent for the treatment of Ewing's sarcoma and related peripheral neuroectodermal tumors.