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Antileukemic Activity of Sulforaphane in Primary Blasts from Patients Affected by Myelo- and Lympho-Proliferative Disorders and in Hypoxic Conditions
Authors:Carmela Fimognari  Eleonora Turrini  Piero Sestili  Cinzia Calcabrini  Giovanni Carulli  Giulia Fontanelli  Martina Rousseau  Giorgio Cantelli-Forti  Patrizia Hrelia
Institution:1. Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Rimini, Italy.; 2. Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino, Italy.; 3. Division of Hematology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.; 4. Department of Pharmacy and BioTechnology, Alma Mater Studiorum-University of Bologna, Bologna, Italy.; Università degli Studi di Firenze, Italy,
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.
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