title: Antileukemic activity of sulforaphane in primary blasts from patients affected by myelo- and lympho-proliferative disorders and in hypoxic conditions.
abstract: Sulforaphane is a dietary isothiocyanate found in cruciferous vegetables showing antileukemic activity. With the purpose of extending the potential clinical impact of sulforaphane in the oncological field, we investigated the antileukemic effect of sulforaphane on blasts from patients affected by different types of leukemia and, taking into account the intrinsically hypoxic nature of bone marrow, on a leukemia cell line (REH) maintained in hypoxic conditions. In particular, we tested sulforaphane on patients with chronic lymphocytic leukemia, acute myeloid leukemia, T-cell acute lymphoblastic leukemia, B-cell acute lymphoblastic leukemia, and blastic NK cell leukemia. Sulforaphane caused a dose-dependent induction of apoptosis in blasts from patients diagnosed with acute lymphoblastic or myeloid leukemia. Moreover, it was able to cause apoptosis and to inhibit proliferation in hypoxic conditions on REH cells. As to its cytotoxic mechanism, we found that sulforaphane creates an oxidative cellular environment that induces DNA damage and Bax and p53 gene activation, which in turn helps trigger apoptosis. On the whole, our results raise hopes that sulforaphane might set the stage for a novel therapeutic principle complementing our growing armature against malignancies and advocate the exploration of sulforaphane in a broader population of leukemic patients.
authors.affiliation: Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Rimini, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Fimognari
authors.affiliation: Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Rimini, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Turrini
authors.affiliation: Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Sestili
authors.affiliation: Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Calcabrini
authors.affiliation: Division of Hematology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Carulli
authors.affiliation: Division of Hematology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Fontanelli
authors.affiliation: Division of Hematology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Rousseau
authors.affiliation: Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Rimini, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Cantelli-Forti
authors.affiliation: Department of Pharmacy and BioTechnology, Alma Mater Studiorum-University of Bologna, Bologna, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Hrelia
mesh_terms: D000693:Anaerobiosis; D000704:Analysis of Variance; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D060833:Cellular Microenvironment / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology* / Q000627:therapeutic use; D008232:Lymphoproliferative Disorders / Q000188:drug therapy*; D009196:Myeloproliferative Disorders / Q000188:drug therapy*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013454:Sulfoxides
chemical_list: D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D017382:Reactive Oxygen Species; D013454:Sulfoxides; C016766:sulforaphane