title: Zyflamend, a polyherbal preparation, inhibits invasion, suppresses osteoclastogenesis, and potentiates apoptosis through down-regulation of NF-kappa B activation and NF-kappa B-regulated gene products.
abstract: Zyflamend, a polyherbal preparation, was designed based on constituents that exhibit antiproliferative, antiinflammatory, antioxidant, antiangiogenic, and apoptotic activities through a mechanism that is not well defined. Because the nuclear factor (NF)-kappaB has been shown to regulate proliferation, invasion, and metastasis of tumor cells, we postulated that Zyflamend modulates the activity of NF-kappa B. To test this hypothesis, we examined the effect of this preparation on NF-kappaB and NF-kappaB-regulated gene products. We found that Zyflamend inhibited receptor activator of NF-kappa B ligand-induced osteoclastogenesis, suppressed tumor necrosis factor (TNF)-induced invasion, and potentiated the cytotoxicity induced by TNF and chemotherapeutic agents, all of which are known to require NF-kappa B activation. Zyflamend suppressed NF-kappa B activation induced by both TNF and cigarette smoke condensate. The expression of NF-kappa B-regulated gene products involved in antiapoptosis (inhibitor-of-apoptosis protein 1/2, Bcl-2, Bcl-xL, FADD-like interleukin-1betaconverting enzyme/caspase-8 inhibitory protein, TNF receptor-associated factor-1, and survivin) and angiogenesis (vascular endothelial growth factor, cyclooxygenase-2, intercellular adhesion molecule, and matrix metalloproteinase-9) was also down-regulated by Zyflamend. This correlated with potentiation of cell death induced by TNF and chemotherapeutic agents. Overall, our results indicate that Zyflamend suppresses osteoclastogenesis, inhibits invasion, and potentiates cytotoxicity through down-regulation of NF-kappa B activation and NF-kappa B-regulated gene products.
authors.affiliation: Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Sandur
authors.forename: Kwang Seok
authors.initials: KS
authors.lastname: Ahn
authors.forename: Haruyo
authors.initials: H
authors.lastname: Ichikawa
authors.forename: Gautam
authors.initials: G
authors.lastname: Sethi
authors.forename: Shishir
authors.initials: S
authors.lastname: Shishodia
authors.forename: Robert A
authors.initials: RA
authors.lastname: Newman
authors.forename: Bharat B
authors.initials: BB
authors.lastname: Aggarwal
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001862:Bone Resorption; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006801:Humans; D016328:NF-kappa B / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; C519312:Zyflamend