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Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
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Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

Published on: May 1, 2020

Perillyl alcohol and genistein differentially regulate PKB/Akt and 4E-BP1 phosphorylation as well as eIF4E/eIF4G

Dennis M Peffley1, Catherine Sharma, Patricia Hentosh

  • 1Department of Biochemistry, Kansas City University of Medicine and Biosciences, 1750 Independence Avenue, Kansas City, MO 64106-1453, USA. dpeffley@odu.edu

Archives of Biochemistry and Biophysics
|July 3, 2007
PubMed

Insights

Plant-derived isoprenoids and genistein differentially affect cancer cell translation pathways. Perillyl alcohol and genistein inhibit key signaling proteins, impacting tumor cell growth and survival.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Isoprenoids, secondary metabolites of plant mevalonate metabolism, are known to inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA translation and induce tumor cell death.
  • The PKB/Akt/mTOR pathway is a critical regulator of mRNA translation and cell growth, making it a target for cancer therapies.

Purpose of the Study:

  • To compare the effects of pure isoprenoids (perillyl alcohol, gamma-tocotrienol) and a mixed isoprenoid-genistein treatment on the PKB/Akt/mTOR pathway.
  • To investigate the impact of these compounds on mRNA translation initiation complex formation (eIF4F).

Main Methods:

  • Cell-based assays using prostate cancer cell lines (DU145, PC-3) and adenocarcinoma cells (Caco2).
  • Western blotting to assess phosphorylation levels of key proteins in the PKB/Akt/mTOR pathway (e.g., 4E-BP1, Akt).
  • Analysis of protein-protein interactions within the eIF4F cap-binding complex.

Main Results:

  • Perillyl alcohol and genistein suppressed 4E-BP1(Ser65) phosphorylation in DU145, PC-3, and Caco2 cells, comparable to PI3K or mTOR inhibitors.
  • Differential effects on 4E-BP1(Thr37) phosphorylation were observed across cell lines and compounds.
  • PKB/Akt activation was enhanced by perillyl alcohol (DU145) and gamma-tocotrienol (PC-3), but suppressed by genistein.
  • Perillyl alcohol disrupted the interaction between eIF4E and eIF4G, crucial for cap-dependent translation.

Conclusions:

  • Pure isoprenoids and genistein exhibit cell- and compound-specific effects on the PKB/Akt/mTOR pathway.
  • These compounds differentially modulate cap-dependent translation initiation in tumor cells.
  • Findings highlight the potential of specific isoprenoids and genistein as targeted agents impacting cancer cell translation.

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