- Dendrogenin A drives LXR to trigger lethal autophagy in cancers.
Dendrogenin A drives LXR to trigger lethal autophagy in cancers.
Nature communications (2017-12-05)
Gregory Segala, Marion David, Philippe de Medina, Mathias C Poirot, Nizar Serhan, François Vergez, Aurelie Mougel, Estelle Saland, Kevin Carayon, Julie Leignadier, Nicolas Caron, Maud Voisin, Julia Cherier, Laetitia Ligat, Frederic Lopez, Emmanuel Noguer, Arnaud Rives, Bruno Payré, Talal Al Saati, Antonin Lamaziere, Gaëtan Despres, Jean-Marc Lobaccaro, Silvere Baron, Cecile Demur, Fabienne de Toni, Clément Larrue, Helena Boutzen, Fabienne Thomas, Jean-Emmanuel Sarry, Marie Tosolini, Didier Picard, Michel Record, Christian Récher, Marc Poirot, Sandrine Silvente-Poirot
PMID29199269
ABSTRACT
Dendrogenin A (DDA) is a newly discovered cholesterol metabolite with tumor suppressor properties. Here, we explored its efficacy and mechanism of cell death in melanoma and acute myeloid leukemia (AML). We found that DDA induced lethal autophagy in vitro and in vivo, including primary AML patient samples, independently of melanoma Braf status or AML molecular and cytogenetic classifications. DDA is a partial agonist on liver-X-receptor (LXR) increasing Nur77, Nor1, and LC3 expression leading to autolysosome formation. Moreover, DDA inhibited the cholesterol biosynthesizing enzyme 3β-hydroxysterol-Δ