Mechanism of the antitumoral activity of deferasirox, an iron chelation agent, on mantle cell lymphoma

Liat Vazana-Barad, Galit Granot, Rahav Mor-Tzuntz, Itai Levi, Martin Dreyling, Ilana Nathan, Ofer Shpilberg

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Mantle cell lymphoma (MCL) characterized by the t(11;14)(q13;q32) translocation, resulting in cyclin D1 overexpression, is one of the most challenging lymphomas to treat. Iron chelators, such as deferasirox, have previously been shown to exhibit anti-proliferative properties; however, their effect on MCL cells has never been investigated. We showed that deferasirox exhibited antitumoral activity against the MCL cell lines HBL-2, Granta-519 and Jeko-1, with 50% inhibitory concentration (IC50) values of 7.99 ± 2.46 μM, 8.93 ± 2.25 μM and 31.86 ± 7.26 μM, respectively. Deferasirox induced apoptosis mediated through caspase-3 activation and decreased cyclin D1 protein levels resulting from increased proteasomal degradation. We also demonstrated down-regulation of phosphor-RB (Ser780) expression, which resulted in increasing levels of the E2F/RB complex and G1/S arrest. Finally, we showed that deferasirox activity was dependent on its iron chelating ability. The present data indicate that deferasirox, by down-regulating cyclin D1 and inhibiting its related signals, may constitute a promising adjuvant therapeutic molecule in the strategy for MCL treatment.

Original languageEnglish
Pages (from-to)851-859
Number of pages9
JournalLeukemia and Lymphoma
Volume54
Issue number4
DOIs
StatePublished - Apr 2013
Externally publishedYes

Keywords

  • Deferasirox
  • Iron chelators
  • Mantle cell lymphoma

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