Potentiating effect of β-caryophyllene on anticancer activity of α-humulene, isocaryophyllene and paclitaxel

Abstract

Abstract β-caryophyllene is a sesquiterpene widely distributed in essential oils of various plants. Several biological activities are attributed to β-caryophyllene, such as anti-inflammatory, antibiotic, antioxidant, anticarcinogenic and local anaesthetic activities. In this work, the potentiating effect of β-caryophyllene on the anticancer activity of α-humulene, isocaryophyllene and paclitaxel against MCF-7, DLD-1 and L-929 human tumour cell lines was evaluated. A non-cytotoxic concentration of β-caryophyllene significantly increased the anticancer activity of α-humulene and isocaryophyllene on MCF-7 cells: α-humulene or isocaryophyllene alone (32 μg mL−1) inhibited cell growth by about 50% and 69%, respectively, compared with 75% and 90% when combined with 10 μg mL−1 β-caryophyllene. Moreover, β-caryophyllene potentiated the anticancer activity of paclitaxel on MCF-7, DLD-1 and L-929 cell lines. The highest potentiating effect was obtained in DLD-1 cells treated with paclitaxel combined with 10 μg mL−1 β-caryophyllene, which increased the paclitaxel activity about 10-fold. The intracellular accumulation of paclitaxel-oregon green was evaluated in combination with concentrations of β-caryophyllene ranging from 2.5 to 40 μg mL−1. β-Caryophyllene (10 μg mL−1) significantly increased the intracellular accumulation of paclitaxel-oregon green (about 64% over controls). Moreover, β-caryophyllene induced intracellular accumulation of calcein but not verapamil, an inhibitor of P-glycoprotein and multidrug resistance related protein transporters, suggesting that β-caryophyllene promotes drug accumulation by a different mechanism of action. These results suggest that β-caryophyllene facilitates the passage of paclitaxel through the membrane and thus potentiates its anticancer activity.