title: Efficacy of panobinostat and marizomib in acute myeloid leukemia and bortezomib-resistant models.
abstract: Current relapse rates in acute myeloid leukemia (AML) highlight the need for new therapeutic strategies. Panobinostat, a novel pan-histone deacetylase inhibitor, and marizomib, a second-generation proteasome inhibitor, are emerging as valuable therapeutic options for hematological malignancies. Here we evaluated apoptotic effects of this combinatorial therapy in AML models and report earlier and higher reactive oxygen species induction and caspase-3 activation and greater caspase-8 dependence than with other combinations. In a bortezomib refractory setting, panobinostat induced high levels of DNA fragmentation, and its action was significantly augmented when combined with marizomib. These data support further study of this combination in hematological malignancies.
authors.affiliation: Department of Pediatrics Research, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0853, Houston, TX 77030, USA; Division of Pediatric Hematology-Oncology, Department of Pediatrics. University of Miami-Miller School of Medicine, Miami, FL 33136.
authors.forename: Fernando F
authors.initials: FF
authors.lastname: Corrales-Medina
authors.affiliation: Department of Pediatrics Research, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0853, Houston, TX 77030, USA; The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas MD Anderson Cancer Center, 6767 Bertner Avenue, Houston, TX 77030, USA.
authors.forename: Christa A
authors.initials: CA
authors.lastname: Manton
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0429, Houston, TX 77030, USA.
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.affiliation: Department of Pediatrics Research, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0853, Houston, TX 77030, USA; The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas MD Anderson Cancer Center, 6767 Bertner Avenue, Houston, TX 77030, USA. Electronic address: jchandra@mdanderson.org.
authors.forename: Joya
authors.initials: J
authors.lastname: Chandra
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005434:Flow Cytometry; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D007783:Lactones / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077767:Panobinostat; D061988:Proteasome Inhibitors / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D004338:Drug Combinations; D006877:Hydroxamic Acids; D007211:Indoles; D007783:Lactones; D061988:Proteasome Inhibitors; D011719:Pyrazines; D011758:Pyrroles; D000069286:Bortezomib; C475865:marizomib; D000077767:Panobinostat; D020169:Caspases
keywords: Acute myeloid leukemia; Bortezomib; Marizomib; Multiple myeloma; Panobinostat