The Water Extract of Juniperus communis L. Induces Cell Death and Sensitizes Cancer Cells to Cytostatic Drugs through p53 and PI3K/Akt Pathways

Int J Mol Sci. 2019 Apr 26;20(9):2054. doi: 10.3390/ijms20092054.

Abstract

Juniper (Juniperus communis L.) is a northern coniferous plant generally used as a spice and for nutritional purposes in foods and drinks. It was previously reported that juniper extract (JE) affects p53 activity, cellular stress, and gene expression induced cell death in human neuroblastoma cells. Therefore, the effects of juniper on p53 and Akt signaling was examined further in A549 lung, 22RV1 and DU145 prostate, and HepG2 liver cancer cells using Western blot, confocal microscopy, and MTT analysis. We found that juniper simultaneously decreased cell viability, activated the p53 pathway, and inactivated the PI3K/Akt pathway. The p53 activation was associated with increased nuclear p53 level. Akt was dephosphorylated, and its inactivation was associated with increased levels of PHLPP1 and PHLPP2 phosphatases. Parallel increases of PARP suggest that JE decreased cell viability by activating cell death. In adtion, JE potentiated the effects of gemcitabine and 5-fluorouracil anticancer drugs. Thus, JE can activate cell death in different cancer cell lines through p53 and Akt pathways.

Keywords: A549 non-small lung cancer cells; Akt; Juniperus communis L.; cell death; p53; plant extract.

MeSH terms

  • A549 Cells
  • Cell Death / drug effects*
  • Cell Survival / drug effects
  • Cytostatic Agents / pharmacology*
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Fluorouracil / pharmacology
  • Gemcitabine
  • Hep G2 Cells
  • Humans
  • Juniperus / chemistry*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Cytostatic Agents
  • Nuclear Proteins
  • Plant Extracts
  • Tumor Suppressor Protein p53
  • Deoxycytidine
  • Proto-Oncogene Proteins c-akt
  • PHLPP1 protein, human
  • PHLPP2 protein, human
  • Phosphoprotein Phosphatases
  • Fluorouracil
  • Gemcitabine

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