Ligand-dependent transcriptional induction of lethal autophagy: A new perspective for cancer treatment
- Resource Type
- Authors
- Marc Poirot; Sandrine Silvente-Poirot; Mathias C. Poirot; Gregory Segala
- Source
- Autophagy
Autophagy, Taylor & Francis, 2018, 14 (3), pp.555-557. ⟨10.1080/15548627.2018.1425059⟩
Autophagy, 2018, 14 (3), pp.555-557. ⟨10.1080/15548627.2018.1425059⟩
- Subject
- Benzylamines
Hydrocarbons, Fluorinated
[SDV]Life Sciences [q-bio]
NR4A1
Apoptosis
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
Ligands
Benzoates
Autophagic Puncta
Mice
Neoplasms
Cytotoxic T cell
cancer cell
Liver X Receptors
[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
Sulfonamides
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology
Myeloid leukemia
[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences
[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
[SDV] Life Sciences [q-bio]
[SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences
Leukemia
[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
LXR
lipids (amino acids, peptides, and proteins)
oxysterol
ChEH
[SDV.CAN]Life Sciences [q-bio]/Cancer
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Biology
[SDV.CAN] Life Sciences [q-bio]/Cancer
Cell Line, Tumor
[SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
medicine
melanoma
Autophagy
Animals
Liver X receptor
[SDV.BC] Life Sciences [q-bio]/Cellular Biology
Molecular Biology
Transcription factor
TFEB
Acute myeloid leukemia
Cell Biology
medicine.disease
zymostenol
Cancer cell
Cancer research
dendrogenin A
[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
Lysosomes
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
- Language
- ISSN
- 1554-8635
1554-8627
International audience; Dendrogenin A (DDA) is a mammalian metabolite that displays anticancer and chemopreventive properties in mice. At the cancer cell level, DDA induces differentiation and death. We investigated herein the nature of DDA cytoxicity in cancer cells. We showed that DDA triggers biochemical and cellular features of macroautophagy/autophagy and that autophagy is cytotoxic. DDA induces both the accumulation of pro-lysosomal sterols and stimulates the expression of regulators of autophagy such as NR4A, LC3 and TFEB through binding to the liver X receptor (LXR), a ligand-dependent transcription factor consisting of 2 isoforms, NR1H2 and NR1H3. These effects are not observed with canonical LXR agonists such as the oxysterol 22(R)-hydroxycholesterol or the synthetic molecules T0901317 and GW3965. DDA effects were measured on melanoma and acute myeloid leukemia cells including patient-derived leukemia cells in vitro and in vivo. Importantly the induction of lethal autophagy kills cells independently of their cytogenetic subgroups and does not differentiate bulk cancer cells from cancer cell progenitors. Together these data show that DDA drives LXR to induce the expression of autophagic genes leading to cancer cells death. This opens up new perspectives for cancer treatment.