Linalool, a plant-derived monoterpene alcohol, reverses doxorubicin resistance in human breast adenocarcinoma cells

Essential oils from various aromatic plants have been reported to exert chemopreventive and/or antitumor effects. In addition, a number of studies have shown the ability of chemopreventive phytochemicals to increase the sensitivity of cancer cells to conventional anticancer drugs. The success of chemotherapeutic agents is often hindered by the development of drug resistance, with multidrug resistant (MDR) phenotypes reported in a number Of tumors, generally involving reduced intracellular drug accumulation due to increased drug efflux by membrane transporters. In the present study, the effects of linalool (LIN), a monoterpene alcohol found in the essential oils from many aromatic plants, on the growth of two human breast adenocarcinoma cell lines, MCF7 WT and multidrug resistant MCF7 Adr(R), were investigated, both as a single agent and in combination with doxorubicin (DOX). The results reported here show that LIN only moderately inhibits cell proliferation; interestingly, however, subtoxic concentrations of LIN potentiate DOX-induced cytotoxicity and pro-apoptotic effects in both cell lines. A significant synergism can be observed in MCF7 Adr(R) cells, which may be due, at least in part, to the ability of LIN to increase DOX accumulation and to induce a decrease in Bcl-x, levels. In summary, the results of the present study suggest that LIN may improve the therapeutic index of anthracyclines in the management of breast cancer, especially in MDR tumors.