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Anticancer effect of linalool via cancer-specific hydroxyl radical generation in human colon cancer
Kenichi Iwasaki1, Yun-Wen Zheng1, Soichiro Murata1
1Kenichi 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.
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.
Insights
The monoterpenoid alcohol linalool demonstrated anticancer effects by inducing cancer-specific oxidative stress and apoptosis in human colon cancer cells. This compound significantly reduced tumor growth in vivo, showing potential for colon cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Colon cancer remains a significant global health challenge.
- Identifying novel therapeutic agents with targeted mechanisms is crucial for improving patient outcomes.
- Natural compounds are increasingly explored for their potential anticancer properties.
Purpose of the Study:
- To elucidate the anticancer mechanisms of linalool in human colon cancer cells.
- To evaluate the efficacy of linalool in reducing colon cancer cell viability and inducing apoptosis.
- To assess the in vivo anticancer effects of linalool on colon cancer xenografts.
Main Methods:
- Cytotoxicity and apoptosis were assessed using WST-8 assays, TUNEL assays, and Annexin V flow cytometry.
- Oxidative stress was investigated via lipid peroxidation markers and electron spin resonance spectroscopy.
- In vivo efficacy was evaluated in SCID mice xenograft models treated with varying doses of linalool.
Main Results:
- Linalool induced cancer cell apoptosis through cancer-specific oxidative stress, evidenced by hydroxyl radical production and lipid peroxidation.
- A high-dose of linalool resulted in a significant 55% reduction in xenograft tumor weight compared to controls (P < 0.05).
- Tumor-specific lipid peroxidation was confirmed in the in vivo models.
Conclusions:
- Linalool exhibits anticancer activity by inducing cancer-specific oxidative stress and apoptosis.
- Linalool demonstrates significant potential as a therapeutic agent for colon cancer.
- Further investigation into linalool's therapeutic applications in oncology is warranted.
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