TAILIEUCHUNG - Báo cáo khoa học: Oligomerized tumor necrosis factor-related apoptosis inducing ligand strongly induces cell death in myeloma cells, but also activates proinflammatory signaling pathways

The oligomerization status of soluble tumor necrosis factor-related apopto-sis inducing ligand (TRAIL) trimers has an overwhelming impact on cell death induction in a cell-type dependent fashion. Thus, we evaluated the ability of single and oligomerized TRAIL trimers to induce cell death in human myeloma cells. In all myeloma cell lines analyzed, oligomerized TRAIL trimers induced caspase activation and complete cell death, whereas non-oligomerized TRAIL trimers showed no or only a modest effect. . | Oligomerized tumor necrosis factor-related apoptosis inducing ligand strongly induces cell death in myeloma cells but also activates proinflammatory signaling pathways Daniela Berg1 Thorsten Stuhmer2 Daniela Siegmund1 Nicole Muller1 Tina Giner3 Oliver Dittrich-Breiholz4 Michael Kracht5 Ralf Bargou2 and Harald Wajant1 1 Division of Molecular InternalMedicine Department of InternalMedicine II University HospitalWurzburg Germany 2 Division of Hematology Department of InternalMedicine II University HospitalWurzburg Germany 3 Department of Dermatology University HospitalWurzburg Germany 4 Institute of Biochemistry MedicalSchoolHannover Germany 5 Rudolf-Buchheim-Institute of Pharmacology University of GieBen Germany Keywords apoptosis JNK multiple myeloma NFkB TRAIL Correspondence H. Wajant Division of Molecular Internal Medicine Department of InternalMedicine II University HospitalWurzburg Roentgenring 11 97070 Wurzburg Germany Fax 49 931 201 71070 Tel 49 931 201 71010 E-mail Received 11 May 2009 revised 10 August 2009 accepted 17 September 2009 doi The oligomerization status of soluble tumor necrosis factor-related apoptosis inducing ligand TRAIL trimers has an overwhelming impact on cell death induction in a cell-type dependent fashion. Thus we evaluated the ability of single and oligomerized TRAIL trimers to induce cell death in human myeloma cells. In all myeloma cell lines analyzed oligomerized TRAIL trimers induced caspase activation and complete cell death whereas non-oligomerized TRAIL trimers showed no or only a modest effect. Caspase activation induced by oligomerized TRAIL was blocked in all cell lines by the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp OMe -fluoromethylketone z-VAD-fmk . Cell death induction was largely blocked in two cell lines by z-VAD-fmk but was only marginally attenuated in three other cell lines indicating that TRAIL induces caspasedependent and .

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