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Diosgenin inhibits osteoclastogenesis, invasion, and proliferation through the downregulation of Akt, I kappa B kinase activation and NF-kappa B-regulated gene expression.
Oncogene. 2006 Mar 09; 25(10):1463-73.O

Abstract

Diosgenin, a steroidal saponin present in fenugreek (Trigonella foenum graecum) and other plants, has been shown to suppress inflammation, inhibit proliferation, and induce apoptosis in a variety of tumor cells, but through a mechanism that is poorly understood. In the present study, we report that diosgenin inhibits receptor-activated nuclear factor-kappaB ligand-induced osteoclastogenesis, suppresses tumor necrosis factor (TNF)-induced invasion, and blocks the proliferation of tumor cells, all activities known to be regulated by NF-kappaB. Diosgenin suppressed TNF-induced NF-kappaB activation as determined by DNA binding, activation of IkappaBalpha kinase, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, and p65 nuclear translocation through inhibition of Akt activation. NF-kappaB-dependent reporter gene expression was also abrogated by diosgenin. TNF-induced expression of NF-kappaB-regulated gene products involved in cell proliferation (cyclin D1, COX-2, c-myc), antiapoptosis (IAP1, Bcl-2, Bcl-X(L), Bfl-1/A1, TRAF1 and cFLIP), and invasion (MMP-9) were also downregulated by the saponin. Diosgenin also potentiated the apoptosis induced by TNF and chemotherapeutic agents. Overall, our results suggest that diosgenin suppresses proliferation, inhibits invasion, and suppresses osteoclastogenesis through inhibition of NF-kappaB-regulated gene expression and enhances apoptosis induced by cytokines and chemotherapeutic agents.

Authors+Show Affiliations

Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

16331273

Citation

Shishodia, S, and B B. Aggarwal. "Diosgenin Inhibits Osteoclastogenesis, Invasion, and Proliferation Through the Downregulation of Akt, I Kappa B Kinase Activation and NF-kappa B-regulated Gene Expression." Oncogene, vol. 25, no. 10, 2006, pp. 1463-73.
Shishodia S, Aggarwal BB. Diosgenin inhibits osteoclastogenesis, invasion, and proliferation through the downregulation of Akt, I kappa B kinase activation and NF-kappa B-regulated gene expression. Oncogene. 2006;25(10):1463-73.
Shishodia, S., & Aggarwal, B. B. (2006). Diosgenin inhibits osteoclastogenesis, invasion, and proliferation through the downregulation of Akt, I kappa B kinase activation and NF-kappa B-regulated gene expression. Oncogene, 25(10), 1463-73.
Shishodia S, Aggarwal BB. Diosgenin Inhibits Osteoclastogenesis, Invasion, and Proliferation Through the Downregulation of Akt, I Kappa B Kinase Activation and NF-kappa B-regulated Gene Expression. Oncogene. 2006 Mar 9;25(10):1463-73. PubMed PMID: 16331273.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diosgenin inhibits osteoclastogenesis, invasion, and proliferation through the downregulation of Akt, I kappa B kinase activation and NF-kappa B-regulated gene expression. AU - Shishodia,S, AU - Aggarwal,B B, PY - 2005/12/7/pubmed PY - 2006/4/14/medline PY - 2005/12/7/entrez SP - 1463 EP - 73 JF - Oncogene JO - Oncogene VL - 25 IS - 10 N2 - Diosgenin, a steroidal saponin present in fenugreek (Trigonella foenum graecum) and other plants, has been shown to suppress inflammation, inhibit proliferation, and induce apoptosis in a variety of tumor cells, but through a mechanism that is poorly understood. In the present study, we report that diosgenin inhibits receptor-activated nuclear factor-kappaB ligand-induced osteoclastogenesis, suppresses tumor necrosis factor (TNF)-induced invasion, and blocks the proliferation of tumor cells, all activities known to be regulated by NF-kappaB. Diosgenin suppressed TNF-induced NF-kappaB activation as determined by DNA binding, activation of IkappaBalpha kinase, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, and p65 nuclear translocation through inhibition of Akt activation. NF-kappaB-dependent reporter gene expression was also abrogated by diosgenin. TNF-induced expression of NF-kappaB-regulated gene products involved in cell proliferation (cyclin D1, COX-2, c-myc), antiapoptosis (IAP1, Bcl-2, Bcl-X(L), Bfl-1/A1, TRAF1 and cFLIP), and invasion (MMP-9) were also downregulated by the saponin. Diosgenin also potentiated the apoptosis induced by TNF and chemotherapeutic agents. Overall, our results suggest that diosgenin suppresses proliferation, inhibits invasion, and suppresses osteoclastogenesis through inhibition of NF-kappaB-regulated gene expression and enhances apoptosis induced by cytokines and chemotherapeutic agents. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/16331273/Diosgenin_inhibits_osteoclastogenesis_invasion_and_proliferation_through_the_downregulation_of_Akt_I_kappa_B_kinase_activation_and_NF_kappa_B_regulated_gene_expression_ L2 - https://doi.org/10.1038/sj.onc.1209194 DB - PRIME DP - Unbound Medicine ER -