Antitumor activity of balsam fir oil: production of reactive oxygen species induced by alpha-humulene as possible mechanism of action.

The antitumor activity of the essential oil of Abies balsamea (balsam fir oil) was evaluated against several solid tumor cell lines including MCF-7, PC-3, A-549, DLD-1, M4BEU and CT-26. Balsam fir oil was found to be active against all the solid tumor cell lines tested, with GI 50 values ranging between 0.76 and 1.7 mg/mL. The oil was analyzed by GC-MS and the cytotoxicity of each oil constituent was determined. Balsam fir oil is essentially constituted of monoterpenes tau; 96 %) and some sesquiterpenes. All the compounds tested were inactive (tau; 250 microM) except for alpha-humulene (GI50 = 55 to 73 microM) which thus seems responsible for the cytotoxicity of the oil. We also tested the cytotoxicity of caryophyllene oxide, which proved inactive, and gamma-caryophyllene which was found to be active against all solid tumor cell lines tested. We evaluated the effects of balsam fir oil and alpha-humulene on the cellular glutathione (GSH) content and on the production of reactive oxygen species (ROS). Balsam fir oil and alpha-humulene induced a dose- and time-dependent decrease in cellular GSH content and an increase in ROS production. These results suggest that GSH depletion and ROS production may be implicated in the cytotoxicity of alpha-humulene and balsam fir oil.