Inhibiting the JNK/ERK signaling pathway with geraniol for attenuating the proliferation of human gastric adenocarcinoma AGS cells.

Abstract

Geraniol, a natural compound found in the essential oils of various aromatic plants, has attracted attention for its probable anticancer effects. The molecular mechanisms of the cell proliferation suppression and apoptosis induction via geraniol in gastric cancer cells (AGS), however, remain unclear. Gastric cancer cells were treated with geraniol, and it was found that the IC50 values were 25 μM/ml, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Results showed that 20 and 25 μM geraniol-induced reactive oxygen species (ROS) production (2'-7'dichlorofluorescin diacetate staining) and decreased mitochondrial membrane potential (rhodamine 123 staining) in AGS cells. Then, it effectively inhibited cell growth and induced apoptosis, confirmed through acridine orange/ethidium bromide, 4',6-diamidino-2-phenylindole, and propidium iodidestaining and molecular marker analysis in AGS cells. Also, geraniol potently diminished caspase-9, Bax, Bcl-2, and caspase-3 expression in AGS cells. We also evaluated the essential mechanism of the cytotoxic effect of geraniol. Moreover, the present study depicted that geraniol-induced cell death through mitochondrial ROS production and inhibited the phosphorylation form of mitogen-activated protein kinase (p38, MAPK, JNK, and ERK1/2) signaling pathway. Taken together, these results concluded that geraniol has a novel therapeutic property against human stomach cancer.