Anticancer effect of linalool via cancer-specific hydroxyl radical generation in human colon cancer

World J Gastroenterol. 2016 Nov 28;22(44):9765-9774. doi: 10.3748/wjg.v22.i44.9765.


Aim: To investigate the anticancer mechanisms of the monoterpenoid alcohol linalool in human colon cancer cells.

Methods: The cytotoxic effect of linalool on the human colon cancer cell lines and a human fibroblast cell line was examined using the WST-8 assay. The apoptosis-inducing effect of linalool was measured using the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and flow cytometry with Annexin V. Oxidative stress was investigated by staining for diphenyl-1-pyrenylphosphine, which is a cellular lipid peroxidation marker, and electron spin resonance spectroscopy. Sixteen SCID mice xenografted with human cancer cells were randomized into 3 groups for in vivo analysis: control and low-dose and high-dose linalool groups. The control group was administered tap water orally every 3 d. The linalool treatment groups were administered 100 or 200 μg/kg linalool solution orally for the same period. All mice were sacrificed under anesthesia 21 d after tumor inoculation, and tumors and organs were collected for immunohistochemistry using an anti-4-hydroxynonenal antibody. Tumor weights were measured and compared between groups.

Results: Linalool induced apoptosis of cancer cells in vitro, following the cancer-specific induction of oxidative stress, which was measured based on spontaneous hydroxyl radical production and delayed lipid peroxidation. Mice in the high-dose linalool group exhibited a 55% reduction in mean xenograft tumor weight compared with mice in the control group (P < 0.05). In addition, tumor-specific lipid peroxidation was observed in the in vivo model.

Conclusion: Linalool exhibited an anticancer effect via cancer-specific oxidative stress, and this agent has potential for application in colon cancer therapy.

Keywords: Colorectal cancer; Electron spin resonance; Linalool; Lipid peroxidation; Oxidative stress.

MeSH terms

  • Acyclic Monoterpenes
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Dose-Response Relationship, Drug
  • HCT116 Cells
  • Humans
  • Hydroxyl Radical / metabolism*
  • Lipid Peroxidation / drug effects
  • Male
  • Mice, SCID
  • Monoterpenes / pharmacology*
  • Oxidants / pharmacology*
  • Oxidative Stress / drug effects*
  • Time Factors
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays


  • Acyclic Monoterpenes
  • Antineoplastic Agents
  • Monoterpenes
  • Oxidants
  • Hydroxyl Radical
  • linalool