Abstract 3733: Combined effect of linalool as component of Humulus lupulus on doxorubicin-induced antitumor activity

Abstract

Abstract [Purpose] Cancer chemotherapy has been applied to advanced tumors and intractable tumors, playing an important role in their treatments. However, there are many problems including the appearance of adverse reactions and acquirement of drug resistance. The increased numbers of medications resulted in a decreased quality of life for the patients. However, food and food components can be used to increase the activity of antitumor agents without increasing the number of medicines. In this study, the effects of some components in Humulus lupulus (Hop) were examined on the doxorubicin (DOX) induced antitumor activity in vitro and in vivo. [Methods] The effects of Hop components (linalool, myrcene, α-humulene, α-caryophyllene) on DOX permeability and DOX cytotoxicity in P388 leukemia cells in vitro were examined. P388 leukemia cells (5 x 105 cells per animal) were transplanted onto the backs of BDF1 mice, and DOX (2.0mg/kg/day x 4 days, i.p.) and linalool (1.0mg/kg/day x 4 days, p.o.) were administered. The solid tumor and normal tissues were removed and measured DOX concentrations in each tissue. [Results and Discussion] In vitro, myrcene, α-humulene and α-caryophyllene did not have beneficial effects on DOX permeability in tumor cells. In contrast, the addition of linalool was shown to significantly promote on DOX influx and increased DOX concentration in tumor cells. The combination of DOX with linalool (0.1 μM) showed 3.5-fold (P<0.05) cytotoxicity, compared to treatment with DOX alone. Therefore, the combined linalool with DOX enhanced DOX cytotoxicity by the increase of DOX concentration in tumor cells. In vivo, the tumor weight in the DOX alone group decreased to 77% of the control level, whereas the combination of linalool with DOX decreased the tumor weight by 53% (P<0.05) of that in DOX alone group. In the tumor, the DOX concentration in the linalool combined group increased by 1.8-fold (P<0.05) compared to DOX alone group. In the normal tissue, the DOX concentration after combined linalool and DOX treatment tended to decrease. In particular, the DOX concentration in the heart decreased by 49% (P<0.05) of that in DOX alone group, expecting that linalool may decrease DOX-induced cardiotoxicity. Thus, the combination of linalool with DOX increased DOX concentration in the tumor, consequently enhanced antitumor activity of DOX. In conclusion, linalool is expected effectiveness as DOX modulator. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3733. doi:1538-7445.AM2012-3733