Potentiating effect of beta-caryophyllene on anticancer activity of alpha-humulene, isocaryophyllene and paclitaxel.
beta-caryophyllene is a sesquiterpene widely distributed in essential oils of various plants. Several biological activities are attributed to beta-caryophyllene, such as anti-inflammatory, antibiotic, antioxidant, anticarcinogenic and local anaesthetic activities. In this work, the potentiating effect of beta-caryophyllene on the anticancer activity of alpha-humulene, isocaryophyllene and paclitaxel against MCF-7, DLD-1 and L-929 human tumour cell lines was evaluated. A non-cytotoxic concentration of beta-caryophyllene significantly increased the anticancer activity of alpha-humulene and isocaryophyllene on MCF-7 cells: alpha-humulene or isocaryophyllene alone (32 microg mL(-1)) inhibited cell growth by about 50% and 69%, respectively, compared with 75% and 90% when combined with 10 microg mL(-1) beta-caryophyllene. Moreover, beta-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 microg mL(-1) beta-caryophyllene, which increased the paclitaxel activity about 10-fold. The intracellular accumulation of paclitaxel-oregon green was evaluated in combination with concentrations of beta-caryophyllene ranging from 2.5 to 40 microg mL(-1). beta-Caryophyllene (10 microg mL(-1)) significantly increased the intracellular accumulation of paclitaxel-oregon green (about 64% over controls). Moreover, beta-caryophyllene induced intracellular accumulation of calcein but not verapamil, an inhibitor of P-glycoprotein and multidrug resistance related protein transporters, suggesting that beta-caryophyllene promotes drug accumulation by a different mechanism of action. These results suggest that beta-caryophyllene facilitates the passage of paclitaxel through the membrane and thus potentiates its anticancer activity.
Legault
Jean
J
Laboratoire LASEVE, Université du Québec à Chicoutimi, Chicoutimi, Québec, Canada. Jean_Legault@uqac.ca
Pichette
André
A
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D020128:Inhibitory Concentration 50; D007739:L Cells; D051379:Mice; D015394:Molecular Structure; D000081222:Monocyclic Sesquiterpenes; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology*; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D000081222:Monocyclic Sesquiterpenes; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C042686:humulene; C024714:caryophyllene; D017239:Paclitaxel