Sandur Santosh K, Ahn Kwang Seok, Ichikawa Haruyo, Sethi Gautam, Shishodia Shishir, Newman Robert A, Aggarwal Bharat B
Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Nutr Cancer. 2007;57(1):78-87. doi: 10.1080/01635580701268295.
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.
Zyflamend是一种多种草药的制剂，它是根据一些成分设计而成的，这些成分通过一种尚未完全明确的机制展现出抗增殖、抗炎、抗氧化、抗血管生成和凋亡活性。由于核因子（NF）-κB已被证明可调节肿瘤细胞的增殖、侵袭和转移，我们推测Zyflamend可调节NF-κB的活性。为了验证这一假设，我们研究了该制剂对NF-κB及NF-κB调节的基因产物的影响。我们发现Zyflamend抑制NF-κB配体诱导的破骨细胞生成，抑制肿瘤坏死因子（TNF）诱导的侵袭，并增强TNF和化疗药物诱导的细胞毒性，而所有这些作用都已知需要NF-κB激活。Zyflamend抑制TNF和香烟烟雾冷凝物诱导的NF-κB激活。参与抗凋亡（凋亡抑制蛋白1/2、Bcl-2、Bcl-xL、FADD样白细胞介素-1β转化酶/半胱天冬酶-8抑制蛋白、TNF受体相关因子-1和生存素）和血管生成（血管内皮生长因子、环氧合酶-2、细胞间黏附分子和基质金属蛋白酶-9）的NF-κB调节基因产物的表达也被Zyflamend下调。这与TNF和化疗药物诱导的细胞死亡增强相关。总体而言，我们的结果表明，Zyflamend通过下调NF-κB激活及NF-κB调节的基因产物来抑制破骨细胞生成、抑制侵袭并增强细胞毒性。
