Tetramethylpyrazine induces reactive oxygen species-based mitochondria-mediated apoptosis in colon cancer cells

BACKGROUND Colon cancer is one of the most common malignancies worldwide, and chemotherapy is a widely used strategy in colon cancer clinical therapy. Chemotherapy resistance is the main cause of recurrence and progression in colon cancer. Thus, novel drugs for treatment are urgently needed. Tetramethylpyrazine (TMP), a component of the traditional Chinese medicine Chuanxiong Hort, has been proven to exhibit a beneficial effect in tumors. AIM To investigate the potential anticancer activity of TMP in colon cancer and the underlying mechanisms. METHODS Colon cancer cells were incubated with different concentrations of TMP. Cell viability was evaluated by crystal violet staining assay, and cell apoptosis was assessed by flow cytometry. Apoptosis-associated protein expression was measured using Western blot analysis. Intracellular reactive oxygen species (ROS) levels were assessed by flow cytometry using DCF fluorescence intensity. Xenografts were established by the subcutaneous injection of colon cancer cells into nude mice; tumor growth was monitored and intracellular ROS was detected in tumors by malondialdehyde assay. RESULTS TMP induced apoptosis of colon cancer cells via the activation of the mitochondrial pathway. TMP increased the generation of intracellular ROS and triggered mitochondria-mediated apoptosis in a caspase-dependent manner. CONCLUSION Our study demonstrates that TMP induces the apoptosis of colon cancer cells and increases the generation of intracellular ROS. TMP triggers mitochondria-mediated apoptosis in a caspase-dependent manner. The accumulation of intracellular ROS is involved in TMP-induced apoptosis. Our findings suggest that TMP may be a potential therapeutic drug for the treatment of colon cancer.