Rosemary extract reduces Akt/mTOR/p70S6K activation and inhibits proliferation and survival of A549 human lung cancer cells

Biomed Pharmacother. 2016 Oct;83:725-732. doi: 10.1016/j.biopha.2016.07.043. Epub 2016 Jul 29.

Abstract

Compounds of plant origin and food components have attracted scientific attention for use as agents for cancer prevention and treatment. Rosemary extract contains polyphenols that were shown to have anti-cancer and other health benefits. The survival pathways of Akt, mammalian target of rapamycin (mTOR) and p70S6K, and the apoptotic protein poly ADP ribose polymerase (PARP) are key modulators of cancer cell growth and survival. In this study, we examined the effects of rosemary extract on proliferation, survival and apoptosis of human non-small cell lung cancer (NSCLC) cells and its influence on signaling events. Human NSCLC adenocarcinoma A549 cells were used. Cell proliferation and clonogenic survival were assessed using specific assays. Immunoblotting was used to examine total and phosphorylated levels of Akt, mTOR and p70S6K, and cleavage of PARP. Rosemary extract dose-dependently inhibited cell proliferation and reduced clonogenic survival of A549 cells, while PARP cleavage, an indicator of apoptosis, was enhanced. Rosemary extract significantly reduced total and phosphorylated/activated Akt, mTOR and p70S6K levels. In conclusion, rosemary extract inhibited proliferation, blocked clonogenic survival, and enhanced apoptosis of A549 lung cancer cells. These effects were associated with inhibition of Akt and downstream mTOR and p70S6K activity. Our data suggest that rosemary extract may have considerable anti-tumor and chemoprevention properties in lung cancer and deserves further systematic investigation in animal models of lung cancer.

Keywords: Akt; Lung cancer; Proliferation; Rosemary extract; Survival; mTOR; p70S6K.

MeSH terms

  • A549 Cells
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Clone Cells
  • Enzyme Activation / drug effects
  • Humans
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / pathology*
  • Models, Biological
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Ribosomal Protein S6 Kinases, 70-kDa
  • Rosmarinus / chemistry*
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Plant Extracts
  • Poly(ADP-ribose) Polymerases
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases, 70-kDa