Abstract
BackgroundDiosgenin, 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 FindingsDiosgenin 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/SignificanceThe 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.
Highlights
Diosgenin is a naturally occurring steroidal saponin present in a variety of plants including fenugreek (Trigonella foenum graecum) and roots of wild yam (Dioscorea villosa) [1]
We further demonstrated that diosgenin suppressed the expression of Matrix metalloproteinases (MMPs)-9 and matrix metalloproteinase-2 (MMP-2) mRNA and protein determined by RT-PCR and Western that diosgenin inhibited the mRNA expression of MMP-2, MMP9, MMP-7 and extracellular inducer of matrix metalloproteinase (EMMPRIN) in a dose-dependent manner
We provided evidences that diosgenin was able to inhibit metastasis in vitro, such as migration and invasion in human prostate cancer PC3 cells, suggesting that diosgenin might possess anti-metastatic potential
Summary
Diosgenin is a naturally occurring steroidal saponin present in a variety of plants including fenugreek (Trigonella foenum graecum) and roots of wild yam (Dioscorea villosa) [1]. Several reports have showed that diosgenin inhibits proliferation and induces apoptosis in a wide variety of tumor cells of human colon [5], osteosarcoma [6], leukemia [7], erythroleukemia [8], breast [9], and liver [10]. Diosgenin inhibits NF-kB activity and NF-kB-regulated gene expression and subsequently reducing proliferation, invasion and osteoclastogenesis [6,13]. A steroidal saponin obtained from fenugreek (Trigonella foenum graecum), was found to exert anticarcinogenic properties, such as inhibiting proliferation and inducing apoptosis in a variety of tumor cells. The aim of the study is to examine the effect of diosgenin on migration and invasion in human prostate cancer PC-3 cells
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