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

• Published in: World journal of gastroenterology Vol. 22; no. 44; pp. 9765 - 9774
• Main Author: 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
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 28.11.2016
• Subjects: Animals; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Basic Study; 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; Lipid peroxidation; Oxidative stress; Electron spin resonance; Linalool; Colorectal cancer
• ISSN: 1007-9327; 2219-2840; 2219-2840
• 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 apoptosisinducing effect of linalool was measured using the terminal deoxynucleotidyl transferase d UTP nickend 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 cancerspecific oxidative stress, and this agent has potential for application in colon cancer therapy.