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

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.

Naringenin modulates the metastasis of human prostate cancer cells by down regulating the matrix metalloproteinases -2/-9 via ROS/ERK1/2 pathways

“…The proteolytic degradation of ECM, a major event in metastasis is mediated by extracellular proteases such as MMPs. MMPs play an important role in various pathologic processes such as angiogenesis and tumor invasion (Kahari and Saarialho-Kere, 1999;Chen et al, 2011). The chief MMPs that are involved in metastasis, MMP-2 and MMP-9 play a crucial role in prostate cancer progression.…”

“…Gallic acid was also reported to inhibit the levels of ERK1/2, the key molecules of the ERK signaling pathway that has been shown to promote tumor invasion and metastasis (Liu et al, 2011). Diosgenin, a naturally occurring steroidal saponin present in a variety of plants including fenugreek (Trigonella foenum graecum) and roots of wild yam (Dioscorea villosa) was observed to inhibit metastasis by inhibiting MMPs and ERK1/2 (Chen et al, 2011).…”

RNA interference: concept to reality in crop improvement

“…Taxol (a produce from Taxus brevifolia) is a mitotic inhibitor, used in the treatment of breast cancer, lung cancer and ovarian cancer. Similarly, diosgenine (Dioscorea deltoidea and Trigonella foenum graecum) inhibits migration and invasion of human prostate cancer PC-3 cells by reducing matrix metalloproteinases expression (Chen et al 2011). It is also used for the commercial synthesis of cortisone, pregnenolone, progesterone, and other steroid products.…”

Isolation and characterization of diosgenin from in vitro cultured tissues of Helicteres isora L

“…The partial synthesis of steroids from plant based precursors is a boon because of the increasing demand for corticosteroids, contraceptives, sex hormones and anabolic steroids since 1960 (Hall and Walker 1991). Recent studies have found that diosgenin has been used in traditional medicine as an antihypercholesterolemia, antihypertriacylglycerolimia antihyperglycemic agent (Chen et al 2011) To date, diosgenin and related steroidal sapogenins were commercially obtained from the tubers of various Dioscorea species; however it is crucial to discover new and alternative sources of these compounds due to decreasing plant resources as well as increasing demand (Savikin et al 1998).…”