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Simvastatin Suppresses Human Breast Cancer Cell Invasion by Decreasing the Expression of Pituitary Tumor-Transforming Gene 1
Statins, or 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, have been widely used to lower cholesterol and prevent cardiovascular diseases. Recent preclinical and clinical studies have shown that statins exert beneficial effects in the management of breast cancer, while the underlying mechanisms remain to be elucidated. Herein, we sought to investigate the effect of statins on the expression of pituitary tumor-transforming gene 1 (PTTG1), a critical gene involved in human breast cancer invasion and metastasis. Our results showed that PTTG1 is highly expressed in malignant Hs578T and MDA-MB-231 breast cancer cel...
Source: Frontiers in Pharmacology - November 4, 2020 Category: Drugs & Pharmacology Source Type: research

Geranylgeraniol prevents the simvastatin-induced PCSK9 expression: Role of the small G protein Rac1
Publication date: August 2017 Source:Pharmacological Research, Volume 122 Author(s): Nicola Ferri, Silvia Marchianò, Maria Giovanna Lupo, Annalisa Trenti, Giuseppe Biondo, Paola Castaldello, Alberto Corsini Statins are known to increase the plasma levels of proprotein convertase subtilisin kexin type 9 (PCSK9) through the activation of the sterol responsive element binding protein (SREBP) pathway due to the inhibition of cholesterol biosynthesis. In the present study, we explore a possible role of the prenylated proteins on the statin-mediated PCSK9 induction in Caco-2 cells. Simvastatin (40μM) induced both PCSK9 mRNA (...
Source: Pharmacological Research - June 10, 2017 Category: Drugs & Pharmacology Source Type: research

Involvement of Pregnane X Receptor in the Impaired Glucose Utilization Induced by Atorvastatin in Hepatocytes.
In conclusion, atorvastatin impaired glucose utilization in hepatocytes via repressing GLUT2 and GCK expressions, which may be partly due to PXR activation. PMID: 26616219 [PubMed - as supplied by publisher]
Source: Biochemical Pharmacology - November 23, 2015 Category: Drugs & Pharmacology Authors: Ling Z, Shu N, Xu P, Wang F, Zhong Z, Sun B, Li F, Zhang M, Zhao K, Tang X, Wang Z, Zhu L, Liu L, Liu X Tags: Biochem Pharmacol Source Type: research

Estrogen receptor mediates simvastatin-stimulated osteogenic effects in bone marrow mesenchymal stem cells.
In this study, we hypothesize that the estrogen receptor (ER) mediates simvastatin-induced osteogenic differentiation. ER antagonists and siRNA were used to determine the involvement of the ER in simvastatin-induced osteogenesis in mouse bone marrow mesenchymal stem cells (D1 cells). Osteogenesis was evaluated by mRNA expression, protein level/activity of osteogenic markers, and mineralization. The estrogen response element (ERE) promoter activity and the ER-simvastatin binding affinity were examined. Our results showed that the simvastatin-induced osteogenic effects were decreased by treatment with ERα antagonists and ER...
Source: Biochemical Pharmacology - September 24, 2015 Category: Drugs & Pharmacology Authors: Chuang SC, Chen CH, Fu YC, Tai IC, Li CJ, Chang LF, Ho ML, Chang JK Tags: Biochem Pharmacol Source Type: research

Autocrine secretion of 15d‐PGJ2 mediates simvastatin‐induced apoptotic burst in human metastatic melanoma cells
Conclusions and ImplicationsWe characterized simvastatin‐induced activation of the 15d‐PGJ2/FABP5 signalling cascades, which triggered an apoptotic burst in melanoma cells but did not affect primary human melanocytes. These data support the rationale for the pharmacological targeting of 15d‐PGJ2 in metastatic melanoma.
Source: British Journal of Pharmacology - December 1, 2014 Category: Drugs & Pharmacology Authors: Christine Wasinger, Martin Künzl, Christoph Minichsdorfer, Christoph Höller, Maria Zellner, Martin Hohenegger Tags: RESEARCH PAPER Source Type: research

Simvastatin induces NFκB/p65 down-regulation and JNK1/c-Jun/ATF-2 activation, leading to matrix metalloproteinase-9 (MMP-9) but not MMP-2 down-regulation in human leukemia cells.
Abstract The aim of the present study was to explore the signaling pathways associated with the effect of simvastatin on matrix metalloproteinase-2 (MMP-2)/MMP-9 expression in human leukemia K562 cells. In sharp contrast to its insignificant effect on MMP-2, simvastatin down-regulated MMP-9 protein expression and mRNA levels in K562 cells. Simvastatin-induced Pin1 down-regulation evoked NFκB/p65 degradation. Meanwhile, simvastatin induced JNK-mediated c-Jun and ATF-2 activation. Over-expression of Pin1 suppressed simvastatin-induced MMP-9 down-regulation. Treatment with SP600125 (a JNK inhibitor) or knock-down of...
Source: Biochemical Pharmacology - October 11, 2014 Category: Drugs & Pharmacology Authors: Chen YJ, Chang LS Tags: Biochem Pharmacol Source Type: research

Autocrine secretion of 15d‐PGJ2 mediates simvastatin induced apoptotic burst in human metastatic melanoma cells
ConclusionWe here delineate simvastatin induced activation of the 15d‐PGJ2/FABP5 signalling cascades, which trigger an apoptotic burst in melanoma cells, while primary human melanocytes were unaffected. These data support new rational ground for pharmacological targeting of 15d‐PGJ2 in metastatic melanoma.
Source: British Journal of Pharmacology - August 4, 2014 Category: Drugs & Pharmacology Authors: Christine Wasinger, Martin Künzl, Christoph Minichsdorfer, Christoph Höller, Maria Zellner, Martin Hohenegger Tags: Research Paper Source Type: research