AIM To investigate the anticancer mechanisms of the monoterpenoid alcohol linalool in human being colon cancer cells. control and low-dose and high-dose linalool organizations. The control group was given tap water orally every 3 d. The linalool treatment organizations were given 100 or 200 μg/kg linalool remedy 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 < 0.05). In addition tumor-specific lipid peroxidation was observed in the model. CONCLUSION Linalool exhibited an anticancer effect cancer-specific oxidative stress and this agent has potential for application in colon cancer therapy. lipid peroxidation. Electron spin resonance (ESR) spectroscopy which LY2784544 enables the real-time visualization of free radicals in live cells revealed that oxidative stress developed PDGFRA immediately after treatment only in cancer cells. This study demonstrated that the natural compound linalool exerted an anticancer effect without causing serious side effects and that the further utilization of ESR may support the application of linalool as a new and cost-effective cancer therapy. INTRODUCTION Colorectal cancer is the fourth most common cause of cancer-related deaths globally and the number of deaths has increased to approximately 700000 annually. Chemotherapy is an LY2784544 effective treatments for colorectal cancer but its side effects such as hair loss low blood counts hand-foot syndrome and neuropathy may depress the patient’s quality of life[2 3 In addition the current anticancer drugs are expensive. Therefore efforts are underway worldwide to identify new effective and inexpensive anticancer compounds with fewer side effects and several types of natural compounds have recently been recognized as possible sources for anticancer drugs[5-9]. This study examined the anticancer effects of the monoterpenoid alcohol linalool which is commonly used as a flavoring agent. Linalool is found abundantly in red wine essential oil of lavender and coriander fruits. Several studies have reported the anticancer potential of linalool against solid tumor cell lines such LY2784544 as gastric cancer lung cancer skin cancer and hepatic cancer (HepG2) as well as several leukemia cell lines. Some of these studies reported that linalool also exerted an apoptotic effect[11 13 induced oxidative stress[12 14 and exhibited immunomodulation. However the mechanism by which linalool exerts its cytotoxic effect has not yet been elucidated. We hypothesized that linalool’s anticancer effects are mediated through the cancer-specific generation of hydroxyl radical followed by apoptosis. We investigated the cytotoxic effects of linalool in LY2784544 the human colon cancer cell line HCT 116 by analyzing the cell death mechanisms and measuring oxidative stress. We focused on the detection of instant reactive oxygen species (ROS) production by using electron spin resonance (ESR) spectroscopy. ESR is a highly sensitive and the most definitive method for the detection of short-lived ROS using the spin-trapping technique such as the hydroxyl radical superoxide and hydroperoxyl radical[16-18]. ESR was developed in the early 1970s and it is often used in research of ischemia-reperfusion injury[19-21] and oxidative stress after exercise. The method is not commonly used in cancer biology studies but it has potential for wide application in cancer screening and therapeutic evaluation in the near future because it is becoming evident that both the ROS levels and redox signaling can affect the phenotypic profile of cancer cells and their responsiveness to therapeutic interventions[23 24 MATERIALS AND METHODS Drugs Linalool (97% pure; Sigma LY2784544 Aldrich St. Louis MO USA) diphenyl-1-pyrenylphosphine(DPPP) (Dojindo Kumamoto Japan) 5 5 (Radical Research Inc. Tokyo Japan) dimethyl sulfoxide (DMSO) (Wako Osaka Japan) and Dulbecco’s modified Eagle’s medium (DMEM) (Wako Osaka Japan) were purchased. Pets and xenograft tumors Six-week-old male serious combined immune insufficiency (SCID) mice (Clea Tokyo Japan) had been maintained in plastic material cages inside a temperature-controlled space on the 12-h light/dark routine with free usage of water and a typical pellet diet through the entire test. After an acclimation amount of 7 d the solid tumor originated by the.