Diosgenin Exerts Antitumor Activity via Downregulation of Skp2 in Breast Cancer Cells

Abstract

Background. Breast cancer is the common malignancy with high morbidity and mortality in women. S-phase kinase-associated protein 2 (Skp2) has been characterized to play an oncogenic role in the breast carcinogenesis and progression. Therefore, inactivation of Skp2 in breast cancer might be a novel approach for fighting breast malignancy. A natural compound diosgenin has been reported to exert anticancer activity in a variety of human cancers. However, the underlying mechanism has not been fully determined. Methods. In this study, we aim to explore whether diosgenin performed antitumor activity via inhibition of Skp2 in breast cancer cells using several methods including MTT, Transwell invasion assay, RT-PCR, western blotting, and transfection. Results. We found that diosgenin inhibited cell viability and stimulated apoptosis. Moreover, we found that diosgenin reduced cell invasion in breast cancer cells. Furthermore, diosgenin inhibited the expression of Skp2 in breast cancer cells. Notably, diosgenin reduced cell viability and motility and induced apoptosis via suppression of Skp2 in breast cancer cells. Conclusion. Our findings revealed that diosgenin could be a potential inhibitor of Skp2 for treating breast cancer.

Anti-Allergic Diarrhea Effect of Diosgenin Occurs via Improving Gut Dysbiosis in a Murine Model of Food Allergy

“…Interestingly, diosgenin at concentrations greater than 5 μM reduced IL-8 and IL-2 production in a concentration-dependent manner ( Figure 6 A,C). As a previous study has reported the cytotoxic effect of diosgenin, the impact of diosgenin on the viability of Caco-2 cells and OVA-primed MLN cells was further explored [ 26 ]. Concordantly, diosgenin at concentrations greater than 20 μM diminished cell viability in a concentration-dependent manner ( Figure 6 B,D).…”

“…A previously described in vitro method for investigating the impact of diosgenin on cells was employed [ 26 ]. Briefly, Caco-2 cells or OVA-primed MLN cells were incubated with various concentrations of diosgenin (0–200 μM) for 14 and 24 h, respectively.…”

“…Briefly, Caco-2 cells or OVA-primed MLN cells were incubated with various concentrations of diosgenin (0–200 μM) for 14 and 24 h, respectively. The supernatants were harvested for cytokine detection, as described above, and the cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, as described previously [ 26 ].…”

Molecular Mechanism by which Diosbulbin B Regulates the TP63 Gene in Triple-Negative Breast Cancer

“…Among these, diosgenin had the highest DL property and OB value. The main component of Dioscorea opposita regulates the Cdc25C-Cdc2-cyclin B pathway in and the mitochondrial-mediated apoptosis of human breast cancer cell lines to induce G2/M phase arrest, and it may be a potential inhibitor of Skp2, with the ability to reduce cell viability and induce apoptosis 14,15 . In addition, diosgenin signi cantly inhibits actin polymerization, Vav2 phosphorylation and Cdc42 activation to inhibit the migration of MDA-MB-231 cells, the conferring antimetastatic potential 16 .…”

Imatinib and GNF-5 Exhibit an Inhibitory Effect on Growth of Hepatocellar Carcinoma Cells by Downregulating S-phase Kinase-associated Protein 2

“…High expression of Skp2 has been observed in various human cancers and is associated with poor prognosis and adverse therapeutic outcomes, suggesting that Skp2 functions as an oncogene [ 7 , 8 ]. Inhibition of Skp2 expression has been shown to exhibit a potent anti-proliferative effect in various cancer models [ 9 - 11 ].…”