Linalool monoterpene exerts potent antitumor effects in OECM 1 human oral cancer cells by inducing sub-G1 cell cycle arrest, loss of mitochondrial membrane potential and inhibition of PI3K/AKT biochemical pathway

J BUON. Jan-Feb 2019;24(1):323-328.


Purpose: Oral cancer is one of the prevalent types of cancer and has been reported to responsible for significant mortality and morbidity. Since treatment options for oral cancer are limited, there is need to explore novel molecules for treatment of oral cancer. In the current study we evaluated the anticancer activity of a plant derived monoterpene, Linalool against oral cancer cell line, OECM-1.

Methods: Cell viability was determined by MTT assay. Apoptosis was detected by DAPI and annexin V/PI staining. Cell cycle analysis was carried out by flow cytometry. Cell migration was assessed by wound healing assay and the expression of the proteins was determined by western blotting.

Results: The results showed that Linalool inhibited the viability of oral cancer OECM-1 cells in a concentration-dependent manner. The IC50 of Linalool against OECM-1 oral cancer cells was 10 µM as compared to its IC50 of 65 µM against non-cancer FR-2 cells. The anticancer effects were due to the induction of the apoptosis and sub-G1 cell cycle arrest. The results of annexin V/PI further revealed that the apoptotic cell populations increased from 2.6% in the control to 61.3% at 20 µM concentrations. It was observed that Linalool decreased the expression of p-PI3K and p-AKT in a concentration-dependent manner. However, the expression of PI3K and AKT remained almost unaltered.

Conclusions: Taken together it was shown that Linalool monoterpene exerted significant anticancer effects in OECM-1 human oral cancer cells via inducing cell cycle arrest, loss of mitochondrial membrane potential (MMP) and suppressing PI3K/AKT signalling pathway.

MeSH terms

  • Acyclic Monoterpenes
  • Cell Line, Tumor
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • Humans
  • Membrane Potential, Mitochondrial / drug effects*
  • Monoterpenes / pharmacology*
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / enzymology
  • Mouth Neoplasms / pathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-akt / metabolism


  • Acyclic Monoterpenes
  • Monoterpenes
  • Phosphoinositide-3 Kinase Inhibitors
  • linalool
  • Proto-Oncogene Proteins c-akt