Effect of linalool as a component of Humulus lupulus on doxorubicin-induced antitumor activity |
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| Institution: | 1. Division of Cytokine Signaling, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan;2. Department of AIDS Research, Institute of Tropical Medicine, G-COE, Nagasaki University, Nagasaki 852-8523, Japan;3. Department of Urology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan;4. Department of Microbiology, National University of Singapore, Singapore;1. George M. O’Brien Benign Urology Center, University of Wisconsin-Madison, 1656 Linden Drive, Madison, WI 53706, USA;2. School of Veterinary Medicine, University of Wisconsin-Madison, 1656 Linden Drive, Madison, WI 53706, USA;3. Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, 1656 Linden Drive, Madison, WI 53706, USA;4. Division of Experimental Therapeutics, Graduate School of Medicine, Kyoto University Yoshida-Konoé-cho, Sakyo, Kyoto 606-8501, Japan;1. Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou 221002, Jiangsu, China;2. Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China;1. Department of Gastroenterology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan 430060, China;2. Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China;3. Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, China |
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| Abstract: | As malignant neoplasm is a major public health problem, there is a need for the development of a novel modulator that enhances antitumor activity and reduces adverse reactions to antitumor agents. In this study, the effects of some volatile oil components in Humulus lupulus on doxorubicin (DOX) permeability in tumor cells and DOX-induced antitumor activity were examined. In vitro, DOX levels in tumor cells by combined linalool as its component significantly increased in the DOX influx system, and the increased effect by linalool on DOX cytotoxicity was shown. In vivo, the combination of DOX with linalool significantly decreased tumor weight compared with that of DOX alone treated group. The promotion of DOX influx level by combined linalool did not depend on energy, whereas it was suppressed by the absence of Na+. This promoting effect was suppressed by the presence of S-(4-nitrobenzyl)-6-thioinosine and inhibited dependently on phlorizin concentration. It is considered that linalool promoted DOX influx in tumor cells because of its action on DOX transport through concentrative Na+-dependent nucleoside transporter 3, which increased DOX concentration in tumor cells and thus enhanced the antitumor activity of DOX. Therefore, linalool as a food component is anticipated to be an effective DOX modulator. |
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