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
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis Regulatory Proteins / metabolism
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Autophagy / drug effects*
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Autophagy / genetics*
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Beclin-1
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Carcinoma, Hepatocellular / genetics*
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Carcinoma, Hepatocellular / pathology*
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Cell Survival / drug effects
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Class I Phosphatidylinositol 3-Kinases / metabolism
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Class III Phosphatidylinositol 3-Kinases / metabolism
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Cyclohexane Monoterpenes
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Cytosol / metabolism
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Liver Neoplasms / genetics*
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Liver Neoplasms / pathology*
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Membrane Proteins / metabolism
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Microtubule-Associated Proteins / metabolism
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Monoterpenes / pharmacology*
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NF-kappa B / metabolism
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Oncogene Protein v-akt / metabolism
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Phagosomes / drug effects
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Phosphorylation / drug effects
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Signal Transduction / drug effects
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Signal Transduction / genetics
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TOR Serine-Threonine Kinases / metabolism
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Tumor Cells, Cultured
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Tumor Suppressor Protein p53 / metabolism
Substances
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Apoptosis Regulatory Proteins
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BECN1 protein, human
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Beclin-1
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Cyclohexane Monoterpenes
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MAP1LC3A protein, human
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Membrane Proteins
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Microtubule-Associated Proteins
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Monoterpenes
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NF-kappa B
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Proto-Oncogene Proteins c-bcl-2
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Tumor Suppressor Protein p53
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alpha phellandrene
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MTOR protein, human
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Class I Phosphatidylinositol 3-Kinases
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Class III Phosphatidylinositol 3-Kinases
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Oncogene Protein v-akt
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TOR Serine-Threonine Kinases