Apoptotic effects and involvement of trpm7 channels of the traditional herbal medicine, Dangkwisoo-san in gastric cancer cells

Abstract

Dangkwisoo-San (DS) is an herbal formula that has been traditionally used for the treatment of pain and blood stagnation caused by physical trauma in Korea. In the present study, the effects of DS in the growth and survival of AGS gastric adenocarcinoma cells and the involvement of Transient Receptor Potential Melastatin (TRPM) 7 channels were investigated. The AGS cells were treated with varying concentrations of DS. Analyses of the sub Gl, caspase-3 and-9 activity and the mitochondrial depolarization were conducted to determine whether AGS cell death occured by apoptosis. Also, to identify the involvement of TRPM7 channels in AGS cell growth and survival, we used Human Embiyonic Kidney (HEK) 293 cells overexpressed with TRPM7 channels. The sub Gl, caspase-3 and 9 activity and the mitochondrial depolarization was increased by DS and this apoptosis was inhibited by SB203580 (a p38 Mitogen Activated Protein Kinase (MAPK) inhibitor) and by a c-jun NH2-terminal kinase (JNK) II inhibitor. Additionally, DS inhibited TRPM7 like currents in AGS cells and in TRPM7 overexpressed HEK 293 cells. Furthermore, tetracycline induced TRPM7 channel overexpressions in HEK 293 cells increased DS-induced cell death. These results suggested that DS inhibits the growth and survival of gastric cancer cells and TRPM7 channel activity and MAPK signaling is involved in the apoptosis of gastric cancer cells. Therefore, DS may be have an anti-cancer effects and a potential drug for treatment of gastric cancer. Both TRPM7 channel and MAPK signaling may play an important role in proliferation of gastric cancer cells.