Planta Med. 2003 May; 69(5): 402-7.

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

Legault J, Dahl W, Debiton E, Pichette A, Madelmont JC.

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.