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Non-conventional rottlerin anticancer properties

E Maioli1, E Daveri2, E Maellaro3

  • 1Dipartimento di Scienze della Vita, Universita' di Siena, Via A. Moro, 53100, Siena, Italy.

Archives of Biochemistry and Biophysics
|March 17, 2018
PubMed

Insights

Rottlerin, a natural compound, shows promise as an anticancer drug by directly inhibiting key cancer-driving molecules like ERK and mTOR. It also disrupts protein translation, leading to cancer cell death.

Area of Science:

  • Natural product chemistry
  • Molecular oncology
  • Cancer therapeutics

Background:

  • Rottlerin is a natural compound with known anticancer properties.
  • Its mechanisms of action primarily involve apoptosis and autophagy induction.
  • Emerging evidence suggests additional pathways contributing to its toxicity.

Purpose of the Study:

  • To review novel anticancer mechanisms of rottlerin.
  • To highlight its direct inhibition of ERK and mTOR.
  • To explore its impact on protein translation and endoplasmic reticulum stress.

Main Methods:

  • Literature review of rottlerin's molecular targets and cellular effects.
  • Analysis of studies investigating rottlerin's role in signaling pathways.
  • Examination of its effects on protein translation machinery.

Main Results:

  • Rottlerin directly inhibits extracellular signal-regulated kinase (ERK) and mechanistic target of rapamycin (mTOR).
  • It dysregulates cap-dependent protein translation via the mTORC1/4EBP1/eIF4E axis.
  • Rottlerin inhibits eukaryotic initiation factor 2 (eIF2), impacting translation under endoplasmic reticulum stress.

Conclusions:

  • Rottlerin exhibits novel anticancer activities beyond apoptosis and autophagy.
  • Direct inhibition of ERK and mTOR, alongside protein translation disruption, are key mechanisms.
  • Rottlerin represents a promising natural lead compound for developing new cancer therapies.

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