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.
Glycoalkaloids are the biologically active secondary metabolites found in many plants, such as potatoes. Glycoalkaloids are produced in leaves, roots, tubers and sprouts of the potato plant, and are involved in host plant resistance to bacteria, fungi, viruses, and insects.1) Several reports have showed that glycoalkaloids suppress the growth of cancer cells in human skin, liver, prostate, breast and colon.2-4) aSolanine, a trisaccharide glycoalkaloid, is one of the main steroidal glycoalkaloids in potatoes (Solanum tuberosum). 1)Recent studies have demonstrated that a-solanine inhibits the growth of human colon (HT29), liver (HepG2), cervical (HeLa), lymphoma (U937), and stomach (AGS and KATO III) cancer cells.3,5) a-Solanine has also been shown to induce apoptosis of human colon cancer cells through the inhibition of extracellular signal regulating kinase (ERK) phosphorylation and activation of caspase-3.6) Therefore, a-solanine may possess the potential for cancer chemotherapeutic action.Melanoma is a skin cancer that arises from the transformation of melanocytes, which are normally found in the basal layer of the epidermis. Melanoma accounts for nearly 4% of skin cancer cases but for 74% of all skin cancer mortalities. 7)Melanoma development and progression have been welldescribed as a sequential process. Following transformation of melanocytes, tumors undergo horizontal or radial initial growth phase followed by a subsequent vertical growth phase, in which melanoma cells infiltrate and invade the dermis and exhibit metastatic potential. 8,9) The conversion of benign to malignant melanoma is characterized by genetic alteration and frequent chromosomal abnormalities.10,11) Therefore, malignant melanoma has served as an excellent model for investigating the molecular changes associated with the metastatic phenotype.Cancer metastasis is a highly coordinated multistep process, in which cancer cells degrade the extracellular matrix (ECM), penetrate through the basement membrane of capillary and lymphatic vessels, intravasate, and then invade and grow in new tissue.12) The process of metastasis is promoted by expressing and secreting various proteolytic enzymes that can degrade most ECM components. Matrix metalloproteinases (MMPs), a family of Zn-dependent endopeptidases, are the major proteases participating in tumor cell migration, spreading, tissue invasion and metastasis.13) Several MMPs, such as MMP-2 and MMP-9, contribute to the process of metastasis.14,15) The activation of these enzymes enables the degradation of ECM by cancer cells, allowing their access to the vasculature, as well as their migration, and invasion into the target organ and development of cancer metastasis. 13)In addition to MMPs, the mitogen-activated protein kinase family members (MAPK) are also known to mediate metastasis. MAPK family members participate in numerous signaling cascades that play important regulatory roles in cell growth, apoptosis, differentiation, and metastasis. 16,17) The diverse MAPK members are activated in response...
In this study, we fabricated a superhydrophilic and underwater superoleophobic protonated melamine sponge for effective separation of water-rich immiscible oil/water mixtures with extremely high separation efficiency. This protonated melamine sponge exhibited excellent antifouling properties and could be used to separate oil/water mixtures continuously for up to 12 h without any increase in the oil content in filtrate. Moreover, our compressed protonated melamine sponge could separate both surfactant-free and -stabilized oil-in-water emulsions with high separation efficiencies. The high performance of this protonated melamine sponge and its efficient, energy- and cost-effective preparation suggest that it has great potential for use in practical applications.
The unstable slope, which is located at Lushan, central Taiwan, slid when heavy rainfall occurred in recent decades, posing a threat to a nearby village. Slope stability analysis in three dimensions is more realistic and can advance comprehension of the sliding mechanism. The landslides caused by two heavy rainfall events are simulated in sequence using finite element modeling. The three-dimensional (3D) modeling is established according to the data of extensive investigations, including field reconnaissance, borehole drilling, laboratory experimentation, and monitoring of groundwater tables and displacements. In particular, it requires skills for the generation of a sliding surface and the division of the 3D model. The difference in lithology and a joint set initiated the instability of the slope, forming the fractures on the slope. The sliding surface with greatest depth over 100 m has not yet extended to the lower slope, resulting in greater displacements on the upper and middle slopes than those on the lower slope. The 3D numerical modeling not only reasonably simulates the displacements induced by the rainfall events, but also enables 3D visualization and details of the sliding mechanism. Also, it is capable of revealing the features that cannot be explained in a 2D analysis.
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