Tetramethylpyrazine regulates breast cancer cell viability, migration, invasion and apoptosis by affecting the activity of Akt and caspase-3.

Tetramethylpyrazine (TMP), an effective component of the traditional Chinese medicine Chuanxiong Hort, has been proven to exhibit a beneficial effect in a number of types of malignant epithelial cancer. However, the mode of action of TMP on breast cancer cells remains unknown. The aim of the present study was to investigate the regulatory effect of TMP on breast cancer cells and its underlying molecular mechanism of action. Different concentrations of TMP were used to treat breast cancer cells, and subsequently, the effects on the viability, apoptosis, and migration and invasion abilities were determined. In addition, the expression and activity levels of the protein kinase B (Akt) signaling pathway and caspase-3 were explored via reverse transcription-quantitative polymerase chain reaction and western blot analysis. The results of the present study revealed that TMP significantly inhibited the viability, migration and invasion rates, and increased the apoptosis of MDA-MB-231 cells in a dose-dependent manner. The minimum effective dose was ~1,600 µM. Additional mechanistic studies demonstrated that 1,600 and 3,200 µM TMP significantly decreased the gene expression and activity of Akt and increased the activity of caspase-3. This mechanism may be responsible for the inhibition of viability, migration and invasion, and activation of apoptosis in breast cancer cells. The results of the present study suggested that TMP may be used in chemotherapy against breast cancer.

Suppression of human breast cancer cells by tectorigenin through downregulation of matrix metalloproteinases and MAPK signaling in vitro.

Breast cancer is a major life­threatening malignancy and is the second highest cause of mortality. The aim of the present study was to investigate the effects of tectorigenin (Tec), a Traditional Chinese Medicine, against human breast cancer cells in vitro. MDA­MB­231 and MCF­7 human breast cancer cells were treated with various concentrations of Tec. Cell proliferation was evaluated using the Cell Counting kit­8 assay, and apoptosis and the cell cycle were examined by flow cytometry. The migratory and invasive abilities of these cells were detected by Transwell and Matrigel assays, respectively. Metastasis­, apoptosis­ and survival­related gene expression levels were measured by reverse transcription­quantitative polymerase chain reaction and western blotting. The results indicated that Tec was able to inhibit the proliferation of MDA­MB­231 and MCF­7 cells in a dose­ and time­dependent manner. Furthermore, Tec treatment induced apoptosis and G0/G1­phase arrest, and inhibited cell migration and invasion. Tec treatment decreased the expression of matrix metalloproteinase (MMP)­2, MMP9, BCL­2, phosphorylated­AKT and components of the mitogen­activated protein kinase (MAPK) signaling pathway, and increased the expression of BCL­2­associated X, cleaved poly [ADP­ribose] polymerase and cleaved caspase­3. In conclusion, Tec treatment suppressed human breast cancer cells through the downregulation of AKT and MAPK signaling and the upregulated expression and/or activity of the caspase family in vitro. Therefore, Tec may be a potential therapeutic drug to treat human breast cancer.