Targeting the β2-adrenergic receptor increases chemosensitivity in multiple myeloma by induction of apoptosis and modulating cancer cell metabolism

Hatice Satilmis, Emma Verheye, Philip Vlummens, Inge Oudaert, Niels Vandewalle, Rong Fan, Jennifer M. Knight, Nathan De Beule, Gamze Ates, Ann Massie, Jerome Moreaux, Anke Maes, Elke De Bruyne, Karin Vanderkerken, Eline Menu, Erica K. Sloan, Kim De Veirman

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5 Citations (Scopus)

Abstract

While multi-drug combinations and continuous treatment have become standard for multiple myeloma, the disease remains incurable. Repurposing drugs that are currently used for other indications could provide a novel approach to improve the therapeutic efficacy of standard multiple myeloma treatments. Here, we assessed the anti-tumor effects of cardiac drugs called β-blockers as a single agent and in combination with commonly used anti-myeloma therapies. Expression of the β2-adrenergic receptor correlated with poor survival outcomes in patients with multiple myeloma. Targeting the β2-adrenergic receptor (β2AR) using either selective or non-selective β-blockers reduced multiple myeloma cell viability, and induced apoptosis and autophagy. Blockade of the β2AR modulated cancer cell metabolism by reducing the mitochondrial respiration as well as the glycolytic activity. These effects were not observed by blockade of β1-adrenergic receptors. Combining β2AR blockade with the chemotherapy drug melphalan or the proteasome inhibitor bortezomib significantly increased apoptosis in multiple myeloma cells. These data identify the therapeutic potential of β2AR-blockers as a complementary or additive approach in multiple myeloma treatment and support the future clinical evaluation of non-selective β-blockers in a randomized controlled trial.

Original languageEnglish
Pages (from-to)69-80
Number of pages12
JournalJournal of Pathology
Volume259
Issue number1
DOIs
Publication statusPublished - Jan 2023

Keywords

  • autophagy
  • chemosensitivity
  • combination therapy
  • glucose
  • metabolism
  • multiple myeloma
  • propranolol
  • β-blocker

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