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Inhibiting the JNK/ERK signaling pathway with geraniol for attenuating the proliferation of human gastric adenocarcinoma AGS cells
Author(s) -
Yang Hongwei,
Liu Guanghui,
Zhao Hongchao,
Dong Xinhua,
Yang Zhen
Publication year - 2021
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22818
Subject(s) - geraniol , apoptosis , chemistry , cancer cell , propidium iodide , p38 mitogen activated protein kinases , reactive oxygen species , mapk/erk pathway , acridine orange , microbiology and biotechnology , cell growth , biochemistry , biology , signal transduction , programmed cell death , cancer , essential oil , chromatography , genetics
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 IC 50 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 (2ʹ‐7ʹdichlorofluorescin 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 iodide staining 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.