Abstract
Matrine, a quinolizidine alkaloid, is commonly employed for treating various viral and inflammatory disorders. Here, we have evaluated matrine for its activity on C-X-C chemokine receptor type 4 (CXCR4) and matrix metalloproteinases (MMP-9/2) expression, and its potential to affect tumor metastasis and invasion. The effects of matrine on CXCR4, MMP-9/2, and nuclear factor κB (NF-κB) activation in lung (A549), prostate (DU145), and pancreas (MIA PaCa-2) cells were investigated by diverse techniques. The expression level of CXCR4 and MMP-9/2 was analyzed by western blot analysis and reverse transcription polymerase chain reaction. NF-κB activation was also evaluated by western blot analysis, electrophoretic mobility shift assay as well as immunocytochemical experiments. Furthermore, we monitored cell invasion and metastasis activities by wound healing and Boyden chamber assays. We noted that matrine induced a down-regulation of CXCR4 and MMP-9/2 at both protein and mRNA levels. In addition, matrine negatively regulated human epidermal growth factor receptor 2 (HER2) and C-X-C Motif Chemokine Ligand 12 (CXCL12)-induced CXCR4 expression. Moreover, NF-κB suppression by matrine led to inhibition of metastatic potential of tumor cells. Our results suggest that matrine can block the cancer metastasis through the negative regulation of CXCR4 and MMP-9/2 and consequently it can be considered as a potential candidate for cancer therapy.
Highlights
Metastasis consists of complex and diverse process that facilitates the expansion of tumor cells from their original site to other organs [1]
A549, DU145, and MIA PaCa-2 cells were treated with matrine or oxymatrine for 24h (Figure 1B)
The results showed that 50 μM of matrine treated cells had more than 80% of cell viability and matrine exhibited low cytotoxicity against A549, DU145, and MIA PaCa-2 cells
Summary
Metastasis consists of complex and diverse process that facilitates the expansion of tumor cells from their original site to other organs [1]. Metastasis of malignant cells can result in rapid degradation of stromal extracellular matrix (ECM) and basement membrane [27] This process can be mediated by various inflammatory enzymes such as MMP-9 and MMP-2 that can promote degradation of diverse ECM components [28,29,30,31,32]. Upregulation of CXCR4 can affect the expression and activity of MMPs and promote cell invasion and migration, [55], we analyzed here the impact of matrine on both CXCR4 as well as MMPs expression. We noticed a substantial downregulation of CXCL12-induced CXCR4 expression by matrine This alkaloid exhibited anti-metastasis activities via affecting the CXCR4 and MMPs levels in human lung, prostate, and pancreatic cancer cells
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