Statins differ in their ability to block NF-kB activation in human blood monocytes

Hilgendorff, Anne; Muth, Heidrun; Parviz, Behnoush; Staubitz, Anne; Haberbosch, Werner; Tillmanns, Harald; Hölschermann, Hans

doi:10.5414/cpp41397

Cited by 116 publications

(82 citation statements)

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“…In contrast to the data of our group demonstrating that VEGF production decreases by statin-treated cancer cells, Takenaka et al, demonstrated that Sv significantly stimulated VEGF to release in a dose-dependent manner in A10 rat vascular smooth muscle cells [30]. The stimulation was, however, visible, at high, micro molar concentrations of the drug.…”

Section: Discussioncontrasting

confidence: 99%

Synergistic Cytotoxic Effect of Statins and Bisphosphonates on Squamous Cell Carcinoma Cell Line

Abdelfattah

Ellithy

Aly

2017

Int J Pharm Pharm Sci

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Objective: The present study aimed at evaluating the in vitro cytotoxic effect of simvastatin (sv) and alendronate (aln) on squamous cell carcinoma cell line (Hep-2 cells). Methods:Hep-2 cells were divided into four groups; Control group where cells were cultured in the routine culture medium. Alendronate Group (A) consisting of cells cultured in aln in its IC 50. Simvastatin Group(S) cultured in sv in its IC 50. And finally, a combined group (A+S) comprising cells cultured in combined IC 50 dose of sv and aln. To assess the effect of these drugs on Hep-2 cells, cell viability was measured in addition to measuring vascular endothelial growth factor (VEGF) expression by Elisa. Results:In all groups, a decrease in the mean viability percentages of the treated Hep-2 cells in relation to control cells was observed in all groups. The combination of both agents exhibited a significant (P-values ˂0.05) synergistic effect on decreasing cell viability and angiogenesis of Hep-2 cells in vitro. VEGF measures in all groups were significantly lower than the control group (P-values ˂ 0.05). The combination of both drugs at their IC 50 doses can lower the VEGF production by Hep-2 cancer cells (P-values ˂ 0.05). Conclusion:A combination of sv and aln in their Ic50 doses has a dramatic effect on lowering the proliferation and VEGF expression in Hep-2 cancer cells cultured in vitro.

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Section: Discussioncontrasting

confidence: 99%

Synergistic Cytotoxic Effect of Statins and Bisphosphonates on Squamous Cell Carcinoma Cell Line

Abdelfattah

Ellithy

Aly

2017

Int J Pharm Pharm Sci

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“…We also found for the first time that simvastatin inhibited not only inducible NF-B activation but also constitutively active NF-B expressed by certain tumor cells. Our results are in agreement with a report that shows that statins can suppress LPS-induced NF-B activation (57). We found for the first time that the NF-B inhibitory activity of the simvastatin could be reversed by mevalonate, indicating that the HMG-CoA pathway also has a role in NF-B activation.…”

Section: Discussionsupporting

confidence: 93%

Simvastatin Potentiates TNF-α-Induced Apoptosis through the Down-Regulation of NF-κB-Dependent Antiapoptotic Gene Products: Role of IκBα Kinase and TGF-β-Activated Kinase-1

Ahn

Sethi

Aggarwal

2007

The Journal of Immunology

101

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Numerous recent reports suggest that statins (hydroxy-3-methylglutaryl-CoA reductase inhibitors) exhibit potential to suppress tumorigenesis through a mechanism that is not fully understood. Therefore, in this article, we investigated the effects of simvastatin on TNF-α-induced cell signaling. We found that simvastatin potentiated the apoptosis induced by TNF-α as indicated by intracellular esterase activity, caspase activation, TUNEL, and annexin V staining. This effect of simvastatin correlated with down-regulation of various gene products that mediate cell proliferation (cyclin D1 and cyclooxygenase-2), cell survival (Bcl-2, Bcl-xL, cellular FLIP, inhibitor of apoptosis protein 1, inhibitor of apoptosis protein 2, and survivin), invasion (matrix mellatoproteinase-9 and ICAM-1), and angiogenesis (vascular endothelial growth factor); all known to be regulated by the NF-κB. We found that simvastatin inhibited TNF-α-induced NF-κB activation, and l-mevalonate reversed the suppressive effect, indicating the role of hydroxy-3-methylglutaryl-CoA reductase. Simvastatin suppressed not only the inducible but also the constitutive NF-κB activation. Simvastatin inhibited TNF-α-induced IκBα kinase activation, which led to inhibition of IκBα phosphorylation and degradation, suppression of p65 phosphorylation, and translocation to the nucleus. NF-κB-dependent reporter gene expression induced by TNF-α, TNFR1, TNFR-associated death domain protein, TNFR-associated factor 2, TGF-β-activated kinase 1, receptor-interacting protein, NF-κB-inducing kinase, and IκB kinase β was abolished by simvastatin. Overall, our results provide novel insight into the role of simvastatin in potentially preventing and treating cancer through modulation of IκB kinase and NF-κB-regulated gene products.

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“…The ability of statins to inhibit NF-B activation in monocytes or ECs exposed to inflammatory stimuli suggests that this transcriptional regulator of Ͼ40 inflammatory genes may be an important statin target (93)(94)(95). The strength of statin NF-B inhibition varies, however, according to drug, cell type, and stimulus (93)(94)(95). In vivo evidence for statin-induced NF-B repression comes from a rabbit model in which administering atorvastatin to atherogenic rabbits reduces NF-B activation in both arterial smooth muscle and macrophages (96).…”

Section: Statins As Antiinflammatory Drugs: Effects On Cells and Tissuesmentioning

confidence: 99%

“…In one study, statins varied by as much as 10-fold in the degree to which they inhibited NF-B activation in stimulated monocytes (cerivastatin Ͼ atorvastatin Ͼ simvastatin Ͼ pravastatin Ͼ lovastatin Ͼ fluvastatin). Given the current limitations of the data, however, it would be premature to make specific formal recommendations about the use of any particular statin as an antiinflammatory agent (94).…”

Section: Statin Trials In Human Inflammatory and Autoimmune Diseasesmentioning

confidence: 99%

Statins as antiinflammatory and immunomodulatory agents: A future in rheumatologic therapy?

Abeles

Pillinger

2006

Arthritis & Rheumatism

136

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Statins differ in their ability to block NF-kB activation in human blood monocytes

Cited by 116 publications

References 0 publications

Synergistic Cytotoxic Effect of Statins and Bisphosphonates on Squamous Cell Carcinoma Cell Line

Synergistic Cytotoxic Effect of Statins and Bisphosphonates on Squamous Cell Carcinoma Cell Line

Simvastatin Potentiates TNF-α-Induced Apoptosis through the Down-Regulation of NF-κB-Dependent Antiapoptotic Gene Products: Role of IκBα Kinase and TGF-β-Activated Kinase-1

Statins as antiinflammatory and immunomodulatory agents: A future in rheumatologic therapy?

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