Antileukemic activity of sulforaphane in primary blasts from patients affected by myelo- and lympho-proliferative disorders and in hypoxic conditions

PLoS One. 2014 Jul 14;9(7):e101991. doi: 10.1371/journal.pone.0101991. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaerobiosis
  • Analysis of Variance
  • Anticarcinogenic Agents / pharmacology*
  • Anticarcinogenic Agents / therapeutic use
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cellular Microenvironment / drug effects
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Humans
  • Isothiocyanates / pharmacology*
  • Isothiocyanates / therapeutic use
  • Lymphoproliferative Disorders / drug therapy*
  • Myeloproliferative Disorders / drug therapy*
  • Reactive Oxygen Species / metabolism
  • Sulfoxides

Substances

  • Anticarcinogenic Agents
  • Isothiocyanates
  • Reactive Oxygen Species
  • Sulfoxides
  • sulforaphane

Grants and funding

This work was supported by Fondazione Cassa di Risparmio di Imola (Italy) and by Fondazione del Monte di Bologna e Ravenna (Italy). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.