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Effect of linalool as a component of Humulus lupulus on doxorubicin-induced antitumor activity.

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (2012-12-12)
Michiko Miyashita, Yasuyuki Sadzuka
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Linalool, 97%
Supelco
Linalool, analytical standard
Sigma-Aldrich
Linalool, ≥97%, FCC, FG
Sigma-Aldrich
L-Linalool, natural, ≥95%, FG
Sigma-Aldrich
(−)-Linalool, ≥95.0% (sum of enantiomers, GC)
Supelco
(−)-Linalool, analytical standard