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

Abstract

AIMTo investigate the anticancer mechanisms of the monoterpenoid alcohol linalool in human colon cancer cells.METHODSThe 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.RESULTSLinalool 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.CONCLUSIONLinalool exhibited an anticancer effect via cancer-specific oxidative stress, and this agent has potential for application in colon cancer therapy.

Oxidative Stress Modulation and ROS-Mediated Toxicity in Cancer: A Review on In Vitro Models for Plant-Derived Compounds

“…Iwasaki et al in a recently published work [ 50 ] studied the anticancer properties of this monoterpenoid alcohol found in more than 200 plant species. The authors exposed HCT116 (colorectal carcinoma) and CCD-18Co (human colon fibroblast) cells to linalool and observed inhibition of cell proliferation by induction of apoptosis via hydroxyl radical-mediated OS.…”

<p>Efficacy of Combination Therapy with Linalool and Doxorubicin Encapsulated by Liposomes as a Two-in-One Hybrid Carrier System for Epithelial Ovarian Carcinoma</p>

“…30 Among these natural products, LN is a terpene alcohol that exists in various plants such as lamiaceae and lauraceae and is known to be cytotoxic against tumor cells. 14 However, the bioavailability of LN is low because of its insoluble properties, thus limiting its utility as an anticancer drug. 14 To overcome this problem, we previously developed an LN-NE formulation as a nanoemulsion-based delivery system.…”

“… 13 Linalool (LN), a natural compound, exhibits antitumor effects by increasing the production of reactive oxygen species (ROS), promoting cell apoptosis due to oxidative stress. 14 LN is composed of a monoterpene tertiary alcohol and can be obtained from certain plants as an essential oil. 15 However, LN is highly insoluble in water due to the nonpolar nature of hydrocarbons, leading to low bioavailability, limiting the use of LN as a chemotherapeutic agent.…”

In vitro analysis of radioprotective effect of monoterpenes

“…In this study, three kinds of monoterpenes: thymol, linalool, and menthol, were and menthol exhibited anti-cancer effects against human tumor cell lines, such as prostate cancer [19,20], malignant melanoma [21], colon cancer [22], and gastric cancer [23]. They suppressed cell growth and induced apoptosis in tumor cells in a time-and dose-dependent manner.…”