Inhibition of cell proliferation and triggering of apoptosis by agrimonolide through MAP kinase (ERK and p38) pathways in human gastric cancer AGS cells

Abstract

Data from the present study showed that agrimonolide exhibited a high anti-proliferation effect against human gastric cancer AGS cells. Flow cytometric analysis revealed that the number of total apoptotic cells increased after the treatment with the agrimonolide in a dose-dependent manner. In addition, it was found that agrimonolide-induced cell apoptosis was associated with the increase in the (Bcl-2 Associated X Protein, BAX)/(B-cell lymphoma-2, Bcl-2) ratio and the activation of cleaved caspase-3. MAPK (p38, c-Jun N-terminal kinase, and ERK1/2) signaling pathways were involved in agrimonolide-induced apoptosis. Cells were exposed to 40 μM of agrimonolide and the level of phospho-ERK/ERK protein was increased to 7.0-fold as compared to the control, and the expression of phospho-p38 protein showed a significant 6.2-fold increase after 24 h incubation, as compared to the control. The employment of protein kinase inhibitors of PD98059 and SB203580, showed the block effects of agrimonolide on the activation of caspase-3 and apoptosis.