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

Abstract

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.

• Authors: Kenichi Iwasaki, Yun-Wen Zheng, Soichiro Murata, Hiromu Ito, Ken Nakayama, Tomohiro Kurokawa, Naoki Sano, Takeshi Nowatari, Myra O Villareal, Yumiko N Nagano, Hiroko Isoda, Hirofumi Matsui, Nobuhiro Ohkohchi
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 22 Issue 44 Pg. 9765-9774 (Nov 28 2016) ISSN: 2219-2840 [Electronic] United States
• PMID: 27956800 (Publication Type: Journal Article)

Chemical References

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

Topics

• Acyclic Monoterpenes
• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Colonic Neoplasms (drug therapy, metabolism, 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