Related Experiment Video

Updated: Jun 22, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Polyunsaturated fatty acids inhibit PI3K activity in a yeast-based model system

Elodie Couplan1, Marie Le Cann, Christelle Le Foll

  • 1INSERM U, Brest, France.

Biotechnology Journal
|June 27, 2009
PubMed

Insights

Dietary polyunsaturated fatty acids (PUFA) can inhibit the phosphatidylinositol 3-kinase (PI3K) pathway, a key regulator of cell growth and a target in cancer therapy. This study shows PUFA alleviate PI3K pathway overactivity, suggesting a potential dietary intervention for cancer.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • The phosphatidylinositol 3-kinase (PI3K) pathway is crucial for regulating cell growth, proliferation, migration, and apoptosis.
  • Hyperactivity of the PI3K pathway, often due to gene mutation or overexpression, is implicated in numerous cancers, making it a significant pharmacological target.
  • Dietary polyunsaturated fatty acids (PUFA) have been suggested to modulate PI3K activity.

Purpose of the Study:

  • To investigate the effects of long-chain polyunsaturated n-3 fatty acids on the PI3K/PTEN/Akt pathway using a reconstituted yeast model.
  • To determine if PUFA can alleviate the toxic effects associated with PI3K pathway hyperactivity.

Main Methods:

  • A yeast-based model was employed to reconstitute the human PI3K/PTEN/Akt pathway.
  • The impact of various PUFA on PI3K activity and associated cellular processes was assessed.
  • Effects on PI3K catalytic subunit protein levels and phosphatidylinositol 4,5-bisphosphate depletion were measured.

Main Results:

  • Various PUFA demonstrated the ability to alleviate toxicity caused by the overexpression of PI3K.
  • PUFA did not significantly alter the steady-state levels of PI3K catalytic subunit proteins (p110alpha) in yeast.
  • Treatment with PUFA significantly reduced the depletion of phosphatidylinositol 4,5-bisphosphate induced by p110alpha overexpression.

Conclusions:

  • Long-chain polyunsaturated n-3 fatty acids can directly inhibit mammalian PI3K activity within an exogenous cellular context (yeast).
  • These findings suggest a direct inhibitory effect of PUFA on PI3K, independent of other mammalian factors.
  • The results highlight the potential of PUFA, abundant in marine foods and fish oils, as a dietary strategy to target PI3K in cancer therapy.

More Related Videos

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry08:07

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

Published on: July 26, 2019

Radiolabeling and Quantification of Cellular Levels of Phosphoinositides by High Performance Liquid Chromatography-coupled Flow Scintillation10:52

Radiolabeling and Quantification of Cellular Levels of Phosphoinositides by High Performance Liquid Chromatography-coupled Flow Scintillation

Published on: January 6, 2016

Related Concept Videos

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 rapamycin-insensitive companion...
Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
Antifungal Agents01:15

Antifungal Agents

Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure—featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups—enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug’s antifungal activity, although weak binding to cholesterol contributes to...