Diosgenin, a Steroidal Saponin, Inhibits Migration and Invasion of Human Prostate Cancer PC-3 Cells by Reducing Matrix Metalloproteinases ExpressionReport as inadecuate




Diosgenin, a Steroidal Saponin, Inhibits Migration and Invasion of Human Prostate Cancer PC-3 Cells by Reducing Matrix Metalloproteinases Expression - Download this document for free, or read online. Document in PDF available to download.

Background

Diosgenin, a steroidal saponin obtained from fenugreek Trigonella foenum graecum, was found to exert anti-carcinogenic properties, such as inhibiting proliferation and inducing apoptosis in a variety of tumor cells. However, the effect of diosgenin on cancer metastasis remains unclear. The aim of the study is to examine the effect of diosgenin on migration and invasion in human prostate cancer PC-3 cells.

Methods and Principal Findings

Diosgenin inhibited proliferation of PC-3 cells in a dose-dependent manner. When treated with non-toxic doses of diosgenin, cell migration and invasion were markedly suppressed by in vitro wound healing assay and Boyden chamber invasion assay, respectively. Furthermore, diosgenin reduced the activities of matrix metalloproteinase-2 MMP-2 and MMP-9 by gelatin zymography assay. The mRNA level of MMP-2 -9 -7 and extracellular inducer of matrix metalloproteinase EMMPRIN were also suppressed while tissue inhibitor of metalloproteinase-2 TIMP-2 was increased by diosgenin. In addition, diosgenin abolished the expression of vascular endothelial growth factor VEGF in PC-3 cells and tube formation of endothelial cells. Our immunoblotting assays indicated that diosgenin potently suppressed the phosphorylation of phosphatidylinositide-3 kinase PI3K, Akt, extracellular signal regulating kinase ERK and c-Jun N-terminal kinase JNK. In addition, diosgenin significantly decreased the nuclear level of nuclear factor kappa B NF-κB, suggesting that diosgenin inhibited NF-κB activity.

Conclusion-Significance

The results suggested that diosgenin inhibited migration and invasion of PC-3 cells by reducing MMPs expression. It also inhibited ERK, JNK and PI3K-Akt signaling pathways as well as NF-κB activity. These findings reveal new therapeutic potential for diosgenin in anti-metastatic therapy.



Author: Pin-Shern Chen , Yuan-Wei Shih, Hsiang-Ching Huang, Hsing-Wen Cheng

Source: http://plos.srce.hr/



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