Role of the ROS/AMPK signaling pathway in tetramethylpyrazine-induced apoptosis in gastric cancer cells

Tetramethylpyrazine (TMPZ) is one of the active compounds extracted from the traditional Chinese medicinal herb Chuanxiong and several studies have shown it to possess anticancer properties. However, its effectiveness in gastric cancer and its cellular mechanisms are relatively unknown. The present study aimed to investigate the effect of TMPZ on SGC7901 cells, and it was demonstrated that a high dose of TMPZ inhibited cell viability and induced apoptosis by stimulating AMP-activated protein kinase (AMPK) through the generation of reactive oxygen species (ROS). Furthermore, TMPZ-induced apoptosis resulted in the sequential events beginning with the translocation of Bax, the collapse of mitochondrial membrane potential (ΔΨm), the release of cytochrome c and the activation of caspase-9 and -3. Each of these events was inhibited by compound C, a pharmacological inhibitor of AMPK. To the best of our knowledge, these results demonstrate for the first time that the induction of apoptosis by TMPZ in gastric cancer cells is associated with the activation of the ROS/AMPK pathway. AMPK activation induces apoptosis through the mitochondrial apoptotic pathway. In addition, these results raise the possibility that TMPZ may have a future therapeutic role in gastric cancer.