Perillyl alcohol and perillic acid induced cell cycle arrest and apoptosis in non small cell lung cancer cells

Cancer Lett. 2007 Nov 18;257(2):216-26. doi: 10.1016/j.canlet.2007.07.020. Epub 2007 Sep 20.


Plant products such as perillyl alcohol have been reported to possess anti-tumor activities against a number of human cancers though the mechanism of action has not yet been elucidated. The effects of perillyl alcohol (POH) and its metabolite perillic acid (PA) on the proliferation of non small cell lung cancer (NSCLC, A549, and H520) cells were investigated. Both POH and PA elicited dose-dependent cytotoxicity, induced cell cycle arrest and apoptosis with increasing expression of bax, p21 and caspase-3 activity in both the cell lines. Combination studies revealed that exposing the cells to an IC50 concentration of POH or PA sensitized the cells to cisplatin and radiation in a dose-dependent manner. These results indicate that POH and PA in combination therapy may have chemotherapeutic value against NSCLC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Apoptosis / radiation effects
  • Blotting, Western
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Caspase 3 / metabolism
  • Cell Cycle / drug effects*
  • Cell Cycle / radiation effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Cisplatin / pharmacology
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cyclohexenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Drug Synergism
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Humans
  • Inhibitory Concentration 50
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Monoterpenes / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Radiation, Ionizing
  • bcl-2-Associated X Protein / metabolism


  • Antineoplastic Agents
  • BAX protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclohexenes
  • Monoterpenes
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • perillyl alcohol
  • perillic acid
  • Caspase 3
  • Cisplatin