The anti-cancer compound Schweinfurthin A targets Osh2 and disrupts lipid metabolism in the yeast model.

@article{Moosavi2019TheAC,
  title={The anti-cancer compound Schweinfurthin A targets Osh2 and disrupts lipid metabolism in the yeast model.},
  author={Behrooz Moosavi and Meng-Qi Gao and Xiao-Lei Zhu and Guangfu Yang},
  journal={Bioorganic chemistry},
  year={2019},
  pages={
          103471
        }
}
Schweinfurthin A (Sch A) is a natural product with a selective and strong anti-cancer effect. Although it is known to target oxysterol binding proteins, the detailed mode of action is not well understood. Here, we provide strong evidence that yeast cells can be used as a eukaryotic model system to decipher the molecular modes of Sch A. We show that Sch A (100 µM) targets Osh2 (a yeast oxysterol binding protein homolog) genetically and taking advantage of computational chemistry indicate that… Expand
1 Citations

References

SHOWING 1-10 OF 57 REFERENCES
Natural products reveal cancer cell dependence on oxysterol-binding proteins.
TLDR
The ORPphilins are powerful probes of OSBP and ORP4L that will be useful in uncovering their cellular functions and their roles in human diseases. Expand
Pleiotropic Effects of a Schweinfurthin on Isoprenoid Homeostasis
TLDR
These studies are the first to demonstrate that a schweinfurthin exerts pleiotropic effects on isoprenoid homeostasis. Expand
A novel approach to the discovery of anti-tumor pharmaceuticals: searching for activators of liponecrosis
TLDR
Yeast can be successfully used as a model organism for high-throughput screens aimed at the discovery of selectively acting anti-tumor small molecules and how this screen consists of searching for chemical compounds capable of increasing the abundance of membrane lipids enriched in unsaturated fatty acids that would therefore be toxic only to rapidly proliferating cells, such as cancer cells and fermenting yeast. Expand
The role of oxysterol-binding protein and its related proteins in cancer.
TLDR
Recent progress in understanding the role of OSBP/ORPs in cancer development is summarized, and how the lipid transfer function ofOSBP/ ORPs may underpin their role in tumorigenesis is discussed. Expand
Use of Yeast as a Model System for Identifying and Studying Anticancer Drugs
TLDR
Yeast is becoming a more widely used system for studying small molecule–protein interactions in general and anticancer agents in particular as a result of decades of research on both the biochemistry and genetics of the budding yeast. Expand
Antiproliferative prenylated stilbenes and flavonoids from Macaranga alnifolia from the Madagascar rainforest.
Bioassay-guided fractionation of an extract of the fruit of Macaranga alnifolia from Madagascar led to the isolation of four new prenylated stilbenes, schweinfurthins E-H (1-4), and one newExpand
Oxysterol-binding proteins: functions in cell regulation beyond lipid metabolism.
TLDR
Small molecular anti-proliferative compounds, ORPphilins, were recently found to target two members of the ORP family, OSBP and ORP4, revealing an essential function of ORPs in cancer cell proliferation and survival. Expand
Bridging the molecular and biological functions of the oxysterol-binding protein family
TLDR
How molecular models of OSBP/ORP-mediated intracellular lipid transport and regulation at membrane contact sites relate to their emerging roles in cellular and organismal functions is reviewed. Expand
Overlapping functions of the yeast oxysterol-binding protein homologues.
TLDR
Findings indicated that OSH genes performed a multitude of nonessential roles defined by specific subsets of the genes and that most shared at least one essential role potentially linked to changes in sterol lipid levels. Expand
New insights into cancer‐related proteins provided by the yeast model
TLDR
The present review summarizes the current knowledge on yeast as a cellular model for investigating the molecular mechanisms of action of the major cancer‐related proteins that, even without yeast orthologues, still recapitulate in yeast some of the key aspects of this cellular pathology. Expand
...
1
2
3
4
5
...