a small molecule smac mimic lbw242 potentiates trail- and anticancer drug-mediated cell death of ovarian cancer cells小分子smac模仿lbw242强化小道,抗癌drug-mediated卵巢癌细胞的细胞死亡.pdfVIP

A Small Molecule SMAC Mimic LBW242 Potentiates TRAIL- and Anticancer Drug-Mediated Cell Death of Ovarian Cancer Cells 1 1 1 1 1 Eleonora Petrucci , Luca Pasquini , Manuela Bernabei , Ernestina Saulle , Mauro Biffoni , 2 2 2 3 3 Fabio Accarpio , Simone Sibio , Angelo Di Giorgio , Violante Di Donato , Assunta Casorelli , 3 1 Pierluigi Benedetti-Panici , Ugo Testa * ` 1 Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanita, Rome, Italy, 2 Department of Surgery Pietro Valdoni, Policlinico Umberto I, University of Rome ‘‘Sapienza’’, Rome, Italy, 3 Department of Obstetrics and Gynaecology, University of Rome ‘‘Sapienza’’, Rome, Italy Abstract Background: Ovarian cancer remains a leading cause of death in women and development of new therapies is essential. Second mitochondria derived activator of caspase (SMAC) has been described to sensitize for apoptosis. We have explored the pro-apoptotic activity of LBW242, a mimic of SMAC/DIABLO, on ovarian cancer cell lines (A2780 cells and its chemoresistant derivative A2780/ADR, SKOV3 and HEY cells) and in primary ovarian cancer cells. The effects of LBW242 on ovarian cancer cell lines and primary ovarian cancer cells was determined by cell proliferation, apoptosis and biochemical assays. Principal Findings: LBW242 added alone elicited only a moderate pro-apoptotic effect; however, it strongly synergizes with tumor necrosis factor-related apoptosis inducing ligand (TRAIL)