title: Anticancer effect of linaloolviacancer-specific hydroxyl radical generation in human colon cancer.
abstract: OBJECTIVE
  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 forin vivoanalysis: 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 cellsin 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 thein vivomodel.
  
  
  CONCLUSIONS
  Linalool exhibited an anticancer effectviacancer-specific oxidative stress, and this agent has potential for application in colon cancer therapy.
authors.affiliation: Kenichi Iwasaki, Yun-Wen Zheng, Soichiro Murata, Ken Nakayama, Tomohiro Kurokawa, Naoki Sano, Takeshi Nowatari, Nobuhiro Ohkohchi, Department of Surgery and Organ Transplantation, Faculty of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki 305-8575, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Iwasaki
authors.affiliation: Kenichi Iwasaki, Yun-Wen Zheng, Soichiro Murata, Ken Nakayama, Tomohiro Kurokawa, Naoki Sano, Takeshi Nowatari, Nobuhiro Ohkohchi, Department of Surgery and Organ Transplantation, Faculty of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki 305-8575, Japan.
authors.forename: Yun-Wen
authors.initials: YW
authors.lastname: Zheng
authors.affiliation: Kenichi Iwasaki, Yun-Wen Zheng, Soichiro Murata, Ken Nakayama, Tomohiro Kurokawa, Naoki Sano, Takeshi Nowatari, Nobuhiro Ohkohchi, Department of Surgery and Organ Transplantation, Faculty of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki 305-8575, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Murata
authors.affiliation: Kenichi Iwasaki, Yun-Wen Zheng, Soichiro Murata, Ken Nakayama, Tomohiro Kurokawa, Naoki Sano, Takeshi Nowatari, Nobuhiro Ohkohchi, Department of Surgery and Organ Transplantation, Faculty of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki 305-8575, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Ito
authors.affiliation: Kenichi Iwasaki, Yun-Wen Zheng, Soichiro Murata, Ken Nakayama, Tomohiro Kurokawa, Naoki Sano, Takeshi Nowatari, Nobuhiro Ohkohchi, Department of Surgery and Organ Transplantation, Faculty of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki 305-8575, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Kenichi Iwasaki, Yun-Wen Zheng, Soichiro Murata, Ken Nakayama, Tomohiro Kurokawa, Naoki Sano, Takeshi Nowatari, Nobuhiro Ohkohchi, Department of Surgery and Organ Transplantation, Faculty of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki 305-8575, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kurokawa
authors.affiliation: Kenichi Iwasaki, Yun-Wen Zheng, Soichiro Murata, Ken Nakayama, Tomohiro Kurokawa, Naoki Sano, Takeshi Nowatari, Nobuhiro Ohkohchi, Department of Surgery and Organ Transplantation, Faculty of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki 305-8575, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Sano
authors.affiliation: Kenichi Iwasaki, Yun-Wen Zheng, Soichiro Murata, Ken Nakayama, Tomohiro Kurokawa, Naoki Sano, Takeshi Nowatari, Nobuhiro Ohkohchi, Department of Surgery and Organ Transplantation, Faculty of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki 305-8575, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nowatari
authors.affiliation: Kenichi Iwasaki, Yun-Wen Zheng, Soichiro Murata, Ken Nakayama, Tomohiro Kurokawa, Naoki Sano, Takeshi Nowatari, Nobuhiro Ohkohchi, Department of Surgery and Organ Transplantation, Faculty of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki 305-8575, Japan.
authors.forename: Myra O
authors.initials: MO
authors.lastname: Villareal
authors.affiliation: Kenichi Iwasaki, Yun-Wen Zheng, Soichiro Murata, Ken Nakayama, Tomohiro Kurokawa, Naoki Sano, Takeshi Nowatari, Nobuhiro Ohkohchi, Department of Surgery and Organ Transplantation, Faculty of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki 305-8575, Japan.
authors.forename: Yumiko N
authors.initials: YN
authors.lastname: Nagano
authors.affiliation: Kenichi Iwasaki, Yun-Wen Zheng, Soichiro Murata, Ken Nakayama, Tomohiro Kurokawa, Naoki Sano, Takeshi Nowatari, Nobuhiro Ohkohchi, Department of Surgery and Organ Transplantation, Faculty of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki 305-8575, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Isoda
authors.affiliation: Kenichi Iwasaki, Yun-Wen Zheng, Soichiro Murata, Ken Nakayama, Tomohiro Kurokawa, Naoki Sano, Takeshi Nowatari, Nobuhiro Ohkohchi, Department of Surgery and Organ Transplantation, Faculty of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki 305-8575, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Matsui
authors.affiliation: Kenichi Iwasaki, Yun-Wen Zheng, Soichiro Murata, Ken Nakayama, Tomohiro Kurokawa, Naoki Sano, Takeshi Nowatari, Nobuhiro Ohkohchi, Department of Surgery and Organ Transplantation, Faculty of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki 305-8575, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ohkohchi
mesh_terms: D000080462:Acyclic Monoterpenes; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D045325:HCT116 Cells; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D016513:Mice, SCID; D039821:Monoterpenes / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000080462:Acyclic Monoterpenes; D000970:Antineoplastic Agents; D039821:Monoterpenes; D016877:Oxidants; D017665:Hydroxyl Radical; C018584:linalool
keywords: Colorectal cancer; Electron spin resonance; Linalool; Lipid peroxidation; Oxidative stress