Dendrogenin A Synergizes with Cytarabine to Kill Acute Myeloid Leukemia Cells In Vitro and In Vivo

Nizar Serhan; Pierre-Luc Mouchel; Philippe de Médina; Gregory Segala; Aurélie Mougel; Estelle Saland; Arnaud Rives; Antonin Lamaziere; Gaëtan Despres; Jean-Emmanuel Sarry; Clément Larrue; François Vergez; Laetitia Largeaud; Michel Record; Christian Récher; Sandrine Silvente-Poirot; Marc Poirot

doi:10.3390/cancers12071725

Journal articles

Dendrogenin A Synergizes with Cytarabine to Kill Acute Myeloid Leukemia Cells In Vitro and In Vivo

Nizar Serhan ¹ Pierre-Luc Mouchel ^{1, 2, 3} Philippe de Médina ¹ Gregory Segala ¹ Aurélie Mougel ¹ Estelle Saland ^{1, 2} Arnaud Rives ^{4, 5} Antonin Lamaziere ⁶ Gaëtan Despres ⁶ Jean-Emmanuel Sarry ^{1, 2} Clément Larrue ^{1, 2} François Vergez ³ Laetitia Largeaud ³ Michel Record ¹ Christian Récher ^{1, 2, 3} Sandrine Silvente-Poirot ¹ Marc Poirot ^{2, 1, *}

* Corresponding author

1 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole

2 CRCT - Centre de Recherches en Cancérologie de Toulouse

3 Service d'Hématologie [IUCT Toulouse]

4 Affichem

5 Dendrogenix [Liège, Belgium]

6 ERL INSERM U1157 - CNRS UMR 7203 - Microorganismes et physiopathologie intestinale

LBM UMR 7203 - Laboratoire des biomolécules

Abstract : Dendrogenin A (DDA) is a mammalian cholesterol metabolite that displays potent antitumor properties on acute myeloid leukemia (AML). DDA triggers lethal autophagy in cancer cells through a biased activation of the oxysterol receptor LXRβ, and the inhibition of a sterol isomerase. We hypothesize that DDA could potentiate the activity of an anticancer drug acting through a different molecular mechanism, and conducted in vitro and in vivo combination tests on AML cell lines and patient primary tumors. We report here results from tests combining DDA with antimetabolite cytarabine (Ara-C), one of the main drugs used for AML treatment worldwide. We demonstrated that DDA potentiated and sensitized AML cells, including primary patient samples, to Ara-C in vitro and in vivo. Mechanistic studies revealed that this sensitization was LXRβ-dependent and was due to the activation of lethal autophagy. This study demonstrates a positive in vitro and in vivo interaction between DDA and Ara-C, and supports the clinical evaluation of DDA in combination with Ara-C for the treatment of AML.

Keywords : Acute myeloid leukemia Dendrogenin A cholesterol metabolism primary cancer cells synergy tumor suppressor.

Document type :

Journal articles

Domain :

Life Sciences [q-bio]

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https://www.hal.inserm.fr/inserm-03084638
Contributor : Marc Poirot <>
Submitted on : Monday, December 21, 2020 - 11:43:34 AM
Last modification on : Wednesday, February 24, 2021 - 11:22:01 AM

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