Transient Receptor Potential Melastatin 7 Channels are Involved in Ginsenoside Rg3-Induced Apoptosis in Gastric Cancer Cells

Abstract

Ginsenosides play a role in a number of physiological and pharmacological functions in the gastrointestinal tract. The aim of this study was to clarify the potential role for transient receptor potential melastatin 7 (TRPM7) channels in ginsenoside Rg3-inhibited growth and survival of AGS cells, the most common human gastric adenocarcinoma cell line. The AGS cells were treated with varying concentrations of Rg3. Sub-G1 analysis, caspase-3 activity and poly(ADP-ribose) polymerase (PARP) cleavage analysis were conducted to determine whether AGS cell death occurs by apoptosis. TRPM7 channel blockers (La(3+) or 2-APB) and small interfering RNA (siRNA) were used in this study to confirm the role of TRPM7 channels. Furthermore, TRPM7 channels were over-expressed in human embryonic kidney (HEK) 293 cells to identify the role of TRPM7 channels in AGS cell growth and survival. The addition of Rg3 to the culture medium inhibited AGS growth and survival. Experimental results showed sub-G1 was markedly increased, caspase-3 activity was elevated, and degree of PARP cleavage was increased. TRPM7 channel blockade, either by La(3+) or 2-APB or by suppressing TRPM7 expression with siRNA, blocked the Rg3-induced inhibition of cell growth and survival. Furthermore, TRPM7 channel over-expression in HEK 293 cells exacerbated Rg3-induced cell death. These findings indicate that ginsenoside Rg3 inhibits the growth and survival of gastric cancer cell which is because of the blockade of TRPM7 channel activity. Therefore, TRPM7 channels may play an important role in the survival of gastric cancer.