Induction of necrosis in human liver tumor cells by α-phellandrene

Nutr Cancer. 2014;66(6):970-9. doi: 10.1080/01635581.2014.936946. Epub 2014 Jul 31.


α-Phellandrene (α-PA) is a component of dietary spices and herbs. The effect of α-PA on anticancer is unclear. This study aims to investigate the effects of α-PA on liver tumor cell death fate. Human liver tumor (J5) cells were incubated with α-PA and analyzed for cell cycle distribution, expression of Bax, Bcl-2, poly (ADP-ribose) polymerase (PARP) protein, and caspase-3 activity of J5 cells, and levels of nitric oxide (NO) production, lactate dehydrogenase (LDH) leakage, and ATP depletion were also analyzed in this study. Results found that α-PA significantly (P < 0.05) decreased the cell viability of J5 cells after 24-h treatment. The cell cycle distribution, Bax, Bcl-2, PARP protein levels, and caspase-3 activity of J5 cells did not change for 24 h after treatment with 30 μM α-PA. Reactive oxygen species levels significantly increased, mitochondrial membrane potential levels significantly decreased when J5 cells were treated with 30 μM α-PA for 24 h (P < 0.05). Thirty μM α-PA significantly (P < 0.05) increased the necrotic cell number, NO production, LDH leakage, and ATP depletion after 24 h of incubation. These results suggest that α-PA induced J5 cell necrosis but not apoptosis, and α-PA-induced necrosis possibly involved ATP depletion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / genetics
  • Adenosine Triphosphate / metabolism
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cyclohexane Monoterpenes
  • Dose-Response Relationship, Drug
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Humans
  • L-Lactate Dehydrogenase / metabolism
  • Membrane Potential, Mitochondrial / drug effects
  • Monoterpenes / pharmacology*
  • Necrosis / metabolism*
  • Nitric Oxide / metabolism
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / metabolism
  • Reactive Oxygen Species / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism


  • Antineoplastic Agents
  • BAX protein, human
  • Cyclohexane Monoterpenes
  • Monoterpenes
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • Nitric Oxide
  • alpha phellandrene
  • Adenosine Triphosphate
  • L-Lactate Dehydrogenase
  • Poly(ADP-ribose) Polymerases
  • CASP3 protein, human
  • Caspase 3