Ligustrazine induces the colorectal cancer cells apoptosis via p53-dependent mitochondrial pathway and cell cycle arrest at the G0/G1 phase

Background: Ligustrazine, active ingredients extracted from the natural herb Ligusticum Chuanxiong Hort, has promising anti-tumor properties on tumor cell lines. However, the potential anti-tumor activity of ligustrazine on colorectal cancer (CRC) cells and the molecular mechanisms have not been elucidated. In this study, we explored the critical functions of ligustrazine on SW480 and CT26 cells at cellular levels. Methods: CCK-8 assay was performed to analyze the cell viability. Flow cytometry analysis was applied to study cell apoptosis and cell cycle. The expressions of cell apoptosis and cell cycle-associated proteins were conducted by western blot and qRT-PCR analysis. Results: Ligustrazine showed significant inhibitory effects on the proliferation of SW480 and CT26 cells. Ligustrazine induced cell apoptosis was associated with the up-regulation of pro-apoptotic protein and the down-regulation of anti-apoptotic protein in an activated mitochondrial-dependent pathway. And it indicated that ligustrazine induced cell cycle arrest by changing the cell cycle distribution, which leads to cell cycle arrest at the G0/G1 phase. Besides, the ligustrazine-induced cell apoptosis and cell cycle arrest were markedly reversed by pifithrin-α (p53 inhibitor), which suggested that ligustrazine-induced cell apoptosis was achieved by regulating p53-dependent mitochondrial pathway and cell cycle arrest at the G0/G1 phase. Conclusions: These findings demonstrated that ligustrazine could induce SW480 and CT26 cells apoptosis via a p53-dependent mitochondrial pathway and cell cycle arrest at the G0/G1 phase. Ligustrazine may serve as a potential anti-cancer agent for CRC.