Related Experiment Video

Updated: Feb 17, 2026

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy
07:20

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy

Published on: January 31, 2025

1.3K

Dendrogenin A drives LXR to trigger lethal autophagy in cancers

Gregory Segala1,2, Marion David1,3, Philippe de Medina4

  • 1UMR 1037-CRCT, Université de Toulouse, INSERM, UPS, Cholesterol Metabolism and Therapeutic Innovations Team, Toulouse, F-31037, France.

Nature Communications
|December 5, 2017
PubMed

Insights

Dendrogenin A (DDA), a cholesterol metabolite, effectively triggers lethal autophagy in melanoma and acute myeloid leukemia (AML) cells. This novel mechanism, involving liver-X-receptor (LXR) activation and sterol pathway inhibition, shows potent anti-tumor activity.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Dendrogenin A (DDA) is a novel cholesterol metabolite identified with potential tumor suppressor functions.
  • Melanoma and acute myeloid leukemia (AML) are significant cancer types with ongoing needs for effective therapeutic strategies.

Purpose of the Study:

  • To investigate the efficacy and cell death mechanisms of Dendrogenin A (DDA) in melanoma and acute myeloid leukemia (AML).
  • To elucidate the molecular pathways targeted by DDA, including its interaction with nuclear receptors and metabolic enzymes.

Main Methods:

  • In vitro and in vivo experiments were conducted using melanoma and AML cell lines, including primary patient samples.
  • DDA's effects on autophagy markers (LC3), nuclear receptor expression (Nur77, Nor1), and cholesterol biosynthesis enzymes (3β-hydroxysterol-Δ8,7-isomerase [D8D7I]) were analyzed.
  • Comparative studies were performed using other liver-X-receptor (LXR) ligands and D8D7I inhibitors.

Main Results:

  • DDA induced lethal autophagy in both melanoma and AML models, irrespective of specific genetic or molecular subtypes.
  • DDA acts as a partial agonist of liver-X-receptor (LXR), upregulating Nur77, Nor1, and LC3, which promotes autolysosome formation.
  • DDA inhibits 3β-hydroxysterol-Δ8,7-isomerase (D8D7I), causing sterol accumulation that cooperates with LXR activation to induce autophagy.
  • The observed mechanism of DDA-induced cell death is distinct from other LXR ligands and D8D7I inhibitors, highlighting DDA's selectivity.

Conclusions:

  • Dendrogenin A (DDA) demonstrates potent anti-tumor activity against melanoma and AML through a unique mechanism of inducing lethal autophagy.
  • DDA's ability to modulate the liver-X-receptor (LXR) and cholesterol biosynthesis pathways offers a novel therapeutic strategy for cancer treatment.
  • The low toxicity and distinct mechanism of DDA warrant further clinical investigation for its application in oncology.

More Related Videos

Evaluating Autophagy Levels in Two Different Pancreatic Cell Models Using LC3 Immunofluorescence08:07

Evaluating Autophagy Levels in Two Different Pancreatic Cell Models Using LC3 Immunofluorescence

Published on: April 28, 2023

2.1K
Live-cell Imaging of Lysosomal Membrane Permeabilization During Necroptosis05:30

Live-cell Imaging of Lysosomal Membrane Permeabilization During Necroptosis

Published on: November 14, 2025

449

Related Concept Videos

Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
4.7K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
8.7K
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
5.9K
Delivery Pathways to the Lysosome01:36

Delivery Pathways to the Lysosome

Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
10.3K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
8.8K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.7K