Induction of α-phellandrene on autophagy in human liver tumor cells

Am J Chin Med. 2015;43(1):121-36. doi: 10.1142/S0192415X15500081. Epub 2015 Feb 4.

Abstract

α-Phellandrene (α-PA) is a cyclic monoterpene. To investigate the induction of autophagy by α-PA and its mechanism, human liver tumor cells (J5) were incubated with α-PA and analyzed for cell viability and the molecular regulation of pre-autophagosome origination and autophagosome formation. According to the results, PI3K-I, mTOR, and Akt protein levels were decreased after α-PA treatment compared to those of the control group (p < 0.05). The phosphorylation of Bcl-2, and PI3K-III, LC3-II and Beclin-1 protein levels in J5 cells were increased after α-PA treatment (p < 0.05). In addition, α-PA up-regulated nuclear p53 and down-regulated cytoplasmic p53 expression in J5 cells. The NF-κB pathway was activated, as indicated by increase in cytosolic phosphorylated IκB, nuclear NF-κB levels, and the DNA-binding activity of NF-κB after α-PA treatment in J5 cells (p < 0.05). These results suggest that α-PA can induce J5 cell autophagy by regulating mTOR and LC-3II expression, p53 signaling, and NF-κB activation in J5 cells.

Keywords: Autophagy; Human Liver Tumor Cells; LC-3II; NF-κB; mTOR; p53; α-Phellandrene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy / drug effects*
  • Autophagy / genetics*
  • Beclin-1
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Survival / drug effects
  • Class I Phosphatidylinositol 3-Kinases / metabolism
  • Class III Phosphatidylinositol 3-Kinases / metabolism
  • Cyclohexane Monoterpenes
  • Cytosol / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology*
  • Membrane Proteins / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Monoterpenes / pharmacology*
  • NF-kappa B / metabolism
  • Oncogene Protein v-akt / metabolism
  • Phagosomes / drug effects
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • Cyclohexane Monoterpenes
  • MAP1LC3A protein, human
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Monoterpenes
  • NF-kappa B
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • alpha phellandrene
  • MTOR protein, human
  • Class I Phosphatidylinositol 3-Kinases
  • Class III Phosphatidylinositol 3-Kinases
  • Oncogene Protein v-akt
  • TOR Serine-Threonine Kinases