Potentiating Effect of Beta-Caryophyllene on Anticancer Activity of Alpha-Humulene, Isocaryophyllene and Paclitaxel

J Pharm Pharmacol. 2007 Dec;59(12):1643-7. doi: 10.1211/jpp.59.12.0005.

Abstract

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.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Humans
  • Inhibitory Concentration 50
  • L Cells
  • Mice
  • Molecular Structure
  • Monocyclic Sesquiterpenes
  • Paclitaxel / chemistry
  • Paclitaxel / pharmacology*
  • Polycyclic Sesquiterpenes
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / pharmacology*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • Monocyclic Sesquiterpenes
  • Polycyclic Sesquiterpenes
  • Sesquiterpenes
  • humulene
  • caryophyllene
  • Paclitaxel