Linalool and
1,8-cineole are plant-derived
isoprenoids with anticancer activities in
lung cancer cells, nevertheless, the cellular and molecular mechanisms of action remain poorly understood. The purpose of this study was to determine the anticancer mechanisms of action of
linalool and
1,8-cineole in
lung adenocarcinoma A549 cells.
Linalool (0-2.0 mM) and
1,8-cineole (0-8.0 mM) inhibited cell proliferation by inducing G0/G1 and/or G2/M cell cycle arrest without affecting cell viability of normal lung WI-38 cells. None of the two
monoterpenes were able to induce apoptosis, as observed by the lack of
caspase-3 and
caspase-9 activation, PARP cleavage, and DNA fragmentation.
Linalool, but not
1,8-cineole, increased
reactive oxygen species production and mitochondrial membrane potential depolarization.
Reactive oxygen species were involved in cell growth inhibition and mitochondrial depolarization induced by
linalool since the
antioxidant N-acetyl-L-cysteine prevented both effects. Besides,
linalool (2.0 mM) and
1,8-cineole (8.0 mM) inhibited A549 cell migration. The combination of each
monoterpene with
simvastatin increased the G0/G1 cell cycle arrest and sensitized cells to apoptosis compared with
simvastatin alone. Our results showed that both
monoterpenes might be promising
anticancer agents with antiproliferative, anti-metastatic, and sensitizer properties for
lung cancer therapy.