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Serhan N, Mouchel PL, Medina P, et al. Dendrogenin A synergizes with Cytarabine to Kill Acute Myeloid Leukemia Cells In Vitro and In Vivo. Cancers (Basel). 2020;12(7)doi: 10.3390/cancers12071725.
Serhan, N., Mouchel, P. L., Medina, P., Segala, G., Mougel, A., Saland, E., Rives, A., Lamaziere, A., Despres, G., Sarry, J. E., Larrue, C., Vergez, F., Largeaud, L., Record, M., Récher, C., Silvente-Poirot, S., & Poirot, M. (2020). Dendrogenin A synergizes with Cytarabine to Kill Acute Myeloid Leukemia Cells In Vitro and In Vivo. Cancers, 12(7), . https://doi.org/10.3390/cancers12071725
Serhan, Nizar, et al. "Dendrogenin A synergizes with Cytarabine to Kill Acute Myeloid Leukemia Cells In Vitro and In Vivo." Cancers vol. 12,7 (2020). doi: https://doi.org/10.3390/cancers12071725
Serhan N, Mouchel PL, Medina P, Segala G, Mougel A, Saland E, Rives A, Lamaziere A, Despres G, Sarry JE, Larrue C, Vergez F, Largeaud L, Record M, Récher C, Silvente-Poirot S, Poirot M. Dendrogenin A synergizes with Cytarabine to Kill Acute Myeloid Leukemia Cells In Vitro and In Vivo. Cancers (Basel). 2020 Jun 29;12(7). doi: 10.3390/cancers12071725. PMID: 32610562; PMCID: PMC7407291.
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Cancers (Basel). 2020 Jun 29;12(7). doi: 10.3390/cancers12071725.

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

Cancers

Nizar Serhan, Pierre-Luc Mouchel, Philippe de Medina, 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

Affiliations

  1. Unité Mixte de Recherche (UMR)1037, Cancer Research Center of Toulouse (CRCT), Institut National de la Santé et de la Recherche Médicale (INSERM) Université de Toulouse, Team Cholesterol Metabolism and Therapeutic Innovations, Equipe labellisée par la Ligue Contre le Cancer, 31037 Toulouse, France.
  2. Cancer Research Center of Toulouse (CRCT), Unité Mixte de Recherche (UMR) 1037 Inserm/Université Toulouse III-Paul Sabatier, ERL5294 Centre national de la recherche scientifique (CNRS), Team Drug Resistance and Oncometabolism in Acute Myeloid Leukemia, 31037 Toulouse, France.
  3. Service d'Hématologie, Institut Universitaire du Cancer de Toulouse-Oncopole, CHU de Toulouse, Université de Toulouse, 31400 Toulouse, France.
  4. AFFICHEM, 31400 Toulouse, France.
  5. Dendrogenix, Liège 4000, Belgium.
  6. Laboratory of Mass Spectrometry, Institut National de la Santé et de la Recherche Médicale (INSERM) ERL 1157, Centre national de la recherche scientifique (CNRS) Unité Mixte de Recherche (UMR) 7203 LBM, Sorbonne Universités-UPMC, CHU Saint-Antoine, 75012 Paris, France.

PMID: 32610562 PMCID: PMC7407291 DOI: 10.3390/cancers12071725

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

Conflict of interest statement

A.R. is employed by the company Dendrogenix. The remaining authors declare no competing financial interests. C.R: Consultancy within the past two years: Jazz Pharma, Daiichi-Sankyo, Astellas, Novartis

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