Inhibition of mTOR/S6K1/4E-BP1 Signaling by Nutraceutical SIRT1 Modulators

Nutr Cancer. 2018 Apr;70(3):490-501. doi: 10.1080/01635581.2018.1446093. Epub 2018 Mar 14.

Abstract

The mTOR pathway plays a crucial role in many human diseases, mostly associated with an over hyperactivity of the mTOR signaling, which makes its inhibitors potentially effective therapeutics. Thus, it is important to consider not only the mTOR pathway, but also all those factors that play a key role in its regulation, such as SIRT1 and AMPK. We previously demonstrated the role of some nutraceutical SIRT1 modulators in AMPK and mTOR pathway, showing the presence of a synergistic effect. Now we take further our research by evaluating the effect of berberine, quercetin, tyrosol, and ferulic acid on the mTOR/S6K1/4E-BP1 signaling, along with the existence of any synergistic effect between the following associations: berberine + tyrosol, tyrosol + ferulic acid, ferulic acid + quercetin. Our results indicate the existence of an important relationship between the substances tested and the pathway of mTOR/S6K1/4E-BP1, a report corroborated by the bond of mTOR with SIRT1/AMPK pathways and by their reciprocal regulation.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Berberine / pharmacology
  • Cell Cycle Proteins
  • Coumaric Acids / pharmacology
  • Dietary Supplements*
  • Drug Synergism
  • HeLa Cells
  • Humans
  • Phenylethyl Alcohol / analogs & derivatives
  • Phenylethyl Alcohol / pharmacology
  • Phosphoproteins / metabolism*
  • Phosphorylation / drug effects
  • Quercetin / pharmacology
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism*
  • Signal Transduction / drug effects
  • Sirtuin 1 / metabolism*
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Coumaric Acids
  • EIF4EBP1 protein, human
  • Phosphoproteins
  • Berberine
  • 4-hydroxyphenylethanol
  • Quercetin
  • ferulic acid
  • MTOR protein, human
  • Ribosomal Protein S6 Kinases, 70-kDa
  • TOR Serine-Threonine Kinases
  • ribosomal protein S6 kinase, 70kD, polypeptide 1
  • SIRT1 protein, human
  • Sirtuin 1
  • Phenylethyl Alcohol