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

Abstract

Abstract. 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.

Novel Homo-Bivalent and Polyvalent Compounds Based on Ligustrazine and Heterocyclic Ring as Anticancer Agents

“…The results revealed that 8e could induce FaDu cells' apoptosis in a dose-dependent manner. This was consistent with other reports showing TMP and its derivatives could induce apoptosis of cancer cells [22][23][24].…”

System Pharmacological Mechanism and Compatibility Laws of Jianghuang from Traditional Chinese Medicine In Blood-Regulating Formulae

“…There are reports that show Chuanxiong (Ligusticum chuanxiong) and Danggui (Angelica sinensis) also can exert anti-tumor effects. Shen J et al [14] used RT-qPCR and western blot analysis to show that CX signi cantly decreased the Akt expression and activity, increased the activity of caspase-3, and was also shown to have anti-tumor effects in several types of cancer. DG can induce gastric cancer cell death through inhibiting mTOR protein and can signi cantly prolong the survival rate of cancer patients [15].…”

Tetramethylpyrazine Induces Apoptosis and Inhibits Proliferation of Hypertrophic Scar-Derived Fibroblasts via Inhibiting the Phosphorylation of AKT

“…It has been generally recognized that traditional Chinese herbal medicines played a unique therapeutic role in the treatment of many diseases (Bhamra et al, 2017;Perry et al, 2018;Li et al, 2019). Tetramethylpyrazine (TMP), an effective component of the traditional Chinese medicine Chuanxiong Rhizoma, which has been used to treat cerebrovascular and cardiovascular diseases, pulmonary diseases and cancer (Huang et al, 2018;Shen et al, 2018). And it was reported that TMP could ameliorate fibrosis in myocardial pulmonary and liver (Wu et al, 2015;Wang et al, 2017;Zhao et al, 2017).…”