scholarly journals Astragaloside IV Enhances Melanogenesis via the AhR-Dependent AKT/GSK-3β/β-Catenin Pathway in Normal Human Epidermal Melanocytes

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Baoyi Liu ◽  
Yongyi Xie ◽  
Zhouwei Wu
Keyword(s):  
Nuclear Translocation ◽  
Astragalus Membranaceus ◽  
Dependent Manner ◽  
Melanin Synthesis ◽  
Astragaloside Iv ◽  
Akt Inhibitor ◽  
Concentration Dependent Manner ◽  
Aryl Hydrocarbon ◽  
Normal Human ◽  
Gsk 3Β

Astragalus membranaceus root has been widely used for repigmentation treatment in vitiligo, but its mechanism is poorly understood. We sought to investigate the effect of astragaloside IV (AS-IV), a main active extract of the Astragalus membranaceus root, on melanin synthesis in normal human epidermal melanocytes (NHEMs) and to elucidate its underlying mechanisms. Melanin content, tyrosinase activity, qPCR, western blot, and immunofluorescence were employed. Specific inhibitors and small interfering RNA were used to investigate the possible pathway. AS-IV stimulated melanin synthesis and upregulated the expression of melanogenesis-related genes in a concentration-dependent manner in NHEMs. AS-IV could activate the aryl hydrocarbon receptor (AhR), and AS-IV-induced melanogenesis was inhibited in si-AhR-transfected NHEMs. In addition, we showed that AS-IV enhanced the phosphorylation of AKT and GSK-3β and nuclear translocation of β-catenin. AS-IV-induced MITF expression upregulation and melanin synthesis were decreased in the presence of β-catenin inhibitor FH353. Furthermore, AhR antagonist CH223191 inhibited the activation of AKT/GSK-3β/β-catenin signaling, whereas the expression of CYP1A1 (marker of AhR activation) was not affected by the AKT inhibitor in AS-IV-exposed NHEMs. Our findings show that AS-IV induces melanogenesis through AhR-dependent AKT/GSK-3β/β-catenin pathway activation and could be beneficial in the therapy for depigmented skin disorders.

scholarly journals Energy determinants GAPDH and NDPK act as genetic modifiers for hepatocyte inclusion formation

2011 ◽  
Vol 195 (2) ◽  
pp. 217-229 ◽  
Author(s):  
Natasha T. Snider ◽  
Sujith V.W. Weerasinghe ◽  
Amika Singla ◽  
Jessica M. Leonard ◽  
Shinichiro Hanada ◽  
...  
Keyword(s):  
Liver Injury ◽  
Human Liver ◽  
Nuclear Translocation ◽  
Nucleoside Diphosphate Kinase ◽  
Isolated Hepatocytes ◽  
Dependent Manner ◽  
Genetic Modifiers ◽  
C3h Mice ◽  
Normal Human ◽  
Human Livers

Genetic factors impact liver injury susceptibility and disease progression. Prominent histological features of some chronic human liver diseases are hepatocyte ballooning and Mallory-Denk bodies. In mice, these features are induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) in a strain-dependent manner, with the C57BL and C3H strains showing high and low susceptibility, respectively. To identify modifiers of DDC-induced liver injury, we compared C57BL and C3H mice using proteomic, biochemical, and cell biological tools. DDC elevated reactive oxygen species (ROS) and oxidative stress enzymes preferentially in C57BL livers and isolated hepatocytes. C57BL livers and hepatocytes also manifested significant down-regulation, aggregation, and nuclear translocation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH). GAPDH knockdown depleted bioenergetic and antioxidant enzymes and elevated hepatocyte ROS, whereas GAPDH overexpression decreased hepatocyte ROS. On the other hand, C3H livers had higher expression and activity of the energy-generating nucleoside-diphosphate kinase (NDPK), and knockdown of hepatocyte NDPK augmented DDC-induced ROS formation. Consistent with these findings, cirrhotic, but not normal, human livers contained GAPDH aggregates and NDPK complexes. We propose that GAPDH and NDPK are genetic modifiers of murine DDC-induced liver injury and potentially human liver disease.

scholarly journals Zanthoxylum nitidum extract attenuates BMP-2-induced inflammation and hyperpermeability

2020 ◽  
Vol 40 (10) ◽  
Author(s):  
Tao Hu ◽  
Zhiwen Luo ◽  
Kai Li ◽  
Shanjin Wang ◽  
Desheng Wu
Keyword(s):  
Side Effects ◽  
Spinal Fusion ◽  
Nuclear Translocation ◽  
Umbilical Vein ◽  
Bone Morphogenetic Protein 2 ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Fluorescent Intensity ◽  
Junction Protein ◽  
Zanthoxylum Nitidum

Abstract Bone morphogenetic protein-2 (BMP-2) is commonly applied in spinal surgery to augment spinal fusion. Nevertheless, its pro-inflammatory potential could induce dangerous side effects such as vascular hyper-permeability, posing the need for manners against this condition. The present study aims to investigate the protective effect of Zanthoxylum nitidum (ZN) on BMP-2-related hyperpermeability and inflammation on the human umbilical vein endothelial cells (HUVECs). The results revealed that, in a concentration-dependent manner, BMP-2 enhanced the production of pro-inflammatory cytokines, including interleukin (IL)-1α, IL-1β, and tumor necrosis factor-α, which were, however, suppressed by ZN. ZN inhibited BMP-2-induced inflammatory response by suppressing the phosphorylation of NF-κBp65 and IκB, and the abnormal nuclear translocation of p65. Moreover, the inhibited expression intercellular tight junction protein VE-cadherin and Occludin caused by BMP-2 was blocked by ZN. The hyper-permeability of HUVECs induced by BMP-2, as expressed as the higher fluorescent intensity of dextran, was also reversed by ZN. Overall, these findings demonstrated that ZN antagonized BMP-2-induced inflammation and hyperpermeability. It could be a therapeutic candidate for the treatment of BMP-2-induced side effects during spinal fusion.

scholarly journals hPMSCs protects against D-galactose-induced oxidative damage of CD4+ T cells through activating Akt-mediated Nrf2 antioxidant signaling 

2020 ◽  
Author(s):  
Yanlian Xiong ◽  
Yueming Wang ◽  
Jiashen Zhang ◽  
Nannan Zhao ◽  
Hengchao Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nuclear Translocation ◽  
Cell Senescence ◽  
Antioxidant Defenses ◽  
Control Group ◽  
Akt Inhibitor ◽  
Gsk 3Β ◽  
T Cell Senescence

Abstract Background: Mesenchymal stem cells (MSCs) was considered as regenerative therapeutic approach in both acute and chronic diseases. However, whether MSCs regulate the antioxidant metabolism of CD4+ T cells and weaken immunosenescence remains unclear. Here, we reported the protective effects of hPMSCs in aging-related CD4+ T cell senescence and identified the underlying mechanisms using a D-gal induced mouse aging model.Methods: In vivo study, 40 male C57BL/6 mice (8 weeks) were randomly divided into four groups: control group, D-gal group, hPMSC group and PBS group. In in vitro experiment, human naive CD4+ T (CD4CD45RA) cells were prepared using a naive CD4+ T cell isolation kit II and pretreated with the Akt inhibitor LY294002 and Nrf2 inhibitor ML385. Then, isolated naive CD4+ T cell were cocultured with hPMSCs for 72 h in the absence or presence of anti-CD3/CD28 Dynabeads and IL-2 as a mitogenic stimulus. Intracellular ROS changes were detected by flow cytometry. The activities of the antioxidant enzymes superoxide dismutase, glutathione peroxidase and catalase were measured by colorimetric analysis. The senescent T cells were detected SA-β-gal stain. The expression of aging related proteins were detected by Western blotting, RT-PCR and confocal microscopy.Results: We found that hPMSC treatment markedly decreased the ROS level, SA-β-gal positive cells number, senescence-associated secretory phenotype (IL-6 and OPN) expression and aging-related protein (P16 and P21) expression in senescent CD4+ T cells. Furthermore, hPMSC treatment effectively upregulated Nrf2 nuclear translocation and the expression of downstream target genes (HO-1, CAT, GCLC and NQO1) in senescent CD4+ T cells. Moreover, in vitro studies revealed that hPMSCs attenuated CD4+ T cell senescence by upregulating the Akt/GSK-3β/Fyn pathway to activate Nrf2 functions. Conversely, the antioxidant effects of hPMSCs were blocked by the Akt inhibitor LY294002 and Nrf2 inhibitor ML385 in senescent CD4+ T cells.Conclusions: Our results indicate that hPMSCs attenuate D-gal induced CD4+ T cell senescence by activating Nrf2-mediated antioxidant defenses and that upregulation of Nrf2 by hPMSCs is regulated via the Akt/GSK-3β/Fyn pathway.

The PTEN/PI3K/Akt signaling pathway mediates HMGB1-induced cell proliferation by regulating the NF-κB/cyclin D1 pathway in mouse mesangial cells

2014 ◽  
Vol 306 (12) ◽  
pp. C1119-C1128 ◽  
Author(s):  
Xiao-Juan Feng ◽  
Shu-Xia Liu ◽  
Chao Wu ◽  
Peng-Peng Kang ◽  
Qing-Juan Liu ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Mesangial Cells ◽  
High Mobility ◽  
Nuclear Factor Κb ◽  
Pyrrolidine Dithiocarbamate ◽  
Chromosomal Protein ◽  
Dependent Manner ◽  
Concentration Dependent Manner

Our previous experiment confirmed that high-mobility group box chromosomal protein 1 (HMGB1) was involved in the pathogenesis of Lupus nephritis (LN) by upregulating the proliferation of the mouse mesangial cell line (MMC) through the cyclin D1/CDK4/p16 system, but the precise mechanism is still unknown. Therefore, in the present study, we demonstrated that HMGB1 induced the proliferation of MMC cells in a time- and concentration-dependent manner, downregulated phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression, increased the level of Akt serine 473 phosphorylation, and induced p65 subunit nuclear translocation. The overexpression of PTEN prevented the upregulation of HMGB1-induced proliferation by blocking the activation of Akt. The knockdown of Akt by siRNA technology and blocking the nuclear factor-κB (NF-κB) pathway using pyrrolidine dithiocarbamate (PDTC) and SN50, inhibitors of NF-κB, both attenuated the HMGB1-induced proliferation by counteracting the activation of the cyclin D1. In addition, while sh-Akt partly blocked the nuclear translocation of the p65 subunit, PDTC did not affect the activation of the Akt induced by HMGB1 in MMC cells. These findings indicate that HMGB1 induced the proliferation of MMC cells by activating the PTEN/phosphoinositide-3-kinase (PI3K)/Akt/NF-κB signaling pathway.

scholarly journals hPMSCs protects against aging-induced oxidative damage of CD4+ T cells through activating Akt-mediated Nrf2 antioxidant signaling

2020 ◽  
Author(s):  
Yanlian Xiong ◽  
Yueming Wang ◽  
Jiashen Zhang ◽  
Nannan Zhao ◽  
Aiping Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nuclear Translocation ◽  
Cell Senescence ◽  
Antioxidant Defenses ◽  
Control Group ◽  
Akt Inhibitor ◽  
Gsk 3Β ◽  
T Cell Senescence

Abstract Background: Mesenchymal stem cells (MSCs) was considered as regenerative therapeutic approach in both acute and chronic diseases. However, whether MSCs regulate the antioxidant metabolism of CD4+ T cells and weaken immunosenescence remains unclear. Here, we reported the protective effects of hPMSCs in aging-related CD4+ T cell senescence and identified the underlying mechanisms using a D-gal induced mouse aging model.Methods: In vivo study, 40 male C57BL/6 mice (8 weeks) were randomly divided into four groups: control group, D-gal group, hPMSC group and PBS group. In in vitro experiment, human naive CD4+ T (CD4CD45RA) cells were prepared using a naive CD4+ T cell isolation kit II and pretreated with the Akt inhibitor LY294002 and Nrf2 inhibitor ML385. Then, isolated naive CD4+ T cell were cocultured with hPMSCs for 72 h in the absence or presence of anti-CD3/CD28 Dynabeads and IL-2 as a mitogenic stimulus. Intracellular ROS changes were detected by flow cytometry. The activities of the antioxidant enzymes superoxide dismutase, glutathione peroxidase and catalase were measured by colorimetric analysis. The senescent T cells were detected SA-β-gal stain. The expression of aging related proteins were detected by Western blotting, RT-PCR and confocal microscopy.Results: We found that hPMSC treatment markedly decreased the ROS level, SA-β-gal positive cells number, senescence-associated secretory phenotype (IL-6 and OPN) expression and aging-related protein (P16 and P21) expression in senescent CD4+ T cells. Furthermore, hPMSC treatment effectively upregulated Nrf2 nuclear translocation and the expression of downstream target genes (HO-1, CAT, GCLC and NQO1) in senescent CD4+ T cells. Moreover, in vitro studies revealed that hPMSCs attenuated CD4+ T cell senescence by upregulating the Akt/GSK-3β/Fyn pathway to activate Nrf2 functions. Conversely, the antioxidant effects of hPMSCs were blocked by the Akt inhibitor LY294002 and Nrf2 inhibitor ML385 in senescent CD4+ T cells.Conclusions: Our results indicate that hPMSCs attenuate D-gal induced CD4+ T cell senescence by activating Nrf2-mediated antioxidant defenses and that upregulation of Nrf2 by hPMSCs is regulated via the Akt/GSK-3β/Fyn pathway.

scholarly journals CCN2 Mediates S1P-Induced Upregulation of COX2 Expression in Human Granulosa-Lutein Cells

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1445
Author(s):  
Hu ◽  
Chang ◽  
Yi ◽  
Liu ◽  
Taylor ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Pge2 Production ◽  
Dependent Manner ◽  
Ccn Family ◽  
Concentration Dependent Manner ◽  
Sphingosine 1 Phosphate ◽  
Small Molecular Inhibitors ◽  
Cox2 Expression ◽  
Ccn2 Expression

CCN1 and CCN2 are members of the CCN family and play essential roles in the regulation of multiple female reproductive functions, including ovulation. Cyclooxygenase-2 (COX2) is a critical mediator of ovulation and can be induced by sphingosine-1-phosphate (S1P) through the S1P1/3-mediated Yes-associated protein (YAP) signaling. However, it is unclear whether CCN1 or CCN2 can mediate S1P-induced upregulation of COX2 expression and increase in prostaglandin E2 (PGE2) production in human granulosa-lutein (hGL) cells. In the present study, we investigated the effects of S1P on the expressions of CCN1 and CCN2 in hGL cells. Additionally, we used a dual inhibition approach (siRNA-mediated silencing and small molecular inhibitors) to investigate the molecular mechanisms of S1P effects. Our results showed that S1P treatment significantly upregulated the expression of CCN1 and CCN2 in a concentration-dependent manner in hGL cells. Additionally, inhibition or silencing of S1P1, but not S1P3, completely abolished the S1P-induced upregulation of CCN2 expression. Furthermore, we demonstrated that S1P-induced nuclear translocation of YAP and inhibition or silencing of YAP completely abolished the S1P-induced upregulation of CCN1 and CCN2 expression. Notably, silencing of CCN2, but not CCN1, completely reversed the S1P-induced upregulation of COX2 expression and the increase in PGE2 production. Thus, CCN2 mediates the S1P-induced upregulation of COX2 expression through the S1P1-mediated signaling pathway in hGL cells. Our findings expand our understanding of the molecular mechanism underlying the S1P-mediated cellular activities in the human ovary.

scholarly journals β-Elemene inhibits the proliferation of primary human airway granulation fibroblasts by down-regulating canonical Wnt/β-catenin pathway

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Cheng Xue ◽  
Ling-Ling Hong ◽  
Jun-Sheng Lin ◽  
Xiang-Yang Yao ◽  
Ding-Hui Wu ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Nuclear Translocation ◽  
Glycogen Synthase ◽  
Smooth Muscle Actin ◽  
Chinese Drug ◽  
Cultured Fibroblasts ◽  
Human Airway ◽  
Normal Human ◽  
Gsk 3Β ◽  
Canonical Wnt

Benign airway stenosis is a clinical challenge because of recurrent granulation tissues. Our previous study proved that a Chinese drug, β-elemene, could effectively inhibit the growth of fibroblasts cultured from hyperplastic human airway granulation tissues, which could slow down the progression of this disease. The purpose of the present study is to find out the mechanism for this effect. We cultured fibroblasts from normal human airway tissues and human airway granulation tissues. These cells were cultured with 160 μg/ml normal saline (NS), different doses of β-elemene, or 10 ng/ml canonical Wnt/β-catenin pathway inhibitor (Dickkopf-1, DKK-1). The proliferation rate of cells and the expression of six molecules involved in canonical Wnt/β-catenin pathway, Wnt3a, glycogen synthase kinase-3β (GSK-3β), β-catenin, α-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), and Collagen I (Col-I), were measured. At last, we used canonical Wnt/β-catenin pathway activator (LiCl) to further ascertain the mechanism of β-elemene. Canonical Wnt/β-catenin pathway is activated in human airway granulation fibroblasts. β-Elemene didn’t affect normal human airway fibroblasts; however, it had a dose–responsive inhibitive effect on the proliferation and expression of Wnt3a, non-active GSK-3β, β-catenin, α-SMA, TGF-β, and Col-I of human airway granulation fibroblasts. More importantly, it had the same effect on the expression and nuclear translocation of active β-catenin. All these effects were similar to 10 ng/ml DKK-1 and could be attenuated by 10 mM LiCl. Thus, β-elemene inhibits the proliferation of primary human airway granulation fibroblasts by down-regulating canonical Wnt/β-catenin pathway. This pathway is possibly a promising target to treat benign tracheobronchial stenosis.

scholarly journals Signaling Events Involved in Macrophage Chemokine Expression in Response to Monosodium Urate Crystals

2004 ◽  
Vol 279 (50) ◽  
pp. 52797-52805 ◽  
Author(s):  
Maritza Jaramillo ◽  
Marianne Godbout ◽  
Paul H. Naccache ◽  
Martin Olivier
Keyword(s):  
Nuclear Translocation ◽  
Gouty Arthritis ◽  
Acute Gout ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Monosodium Urate ◽  
Inhibitory Protein ◽  
Concentration Dependent Manner ◽  
Chemokine Production ◽  
Msu Crystals

Chemokine production has been associated with leukocyte infiltration into the joint during gouty arthritis, and monosodium urate (MSU) crystals, the causative agent of this arthropathy, have been shown to modulate their expression. In the present study, we investigated the transductional mechanisms underlying this cellular regulation in the murine macrophage cell line B10R. We report that MSU crystals rapidly and transiently increase mRNA levels of various chemokines in a concentration-dependent manner. Examination of second messenger activation revealed that macrophage exposure to MSU crystals led to MEK1/2, ERK1/2, and inhibitory protein κBα phosphorylation as well as to NF-κB and AP-1 nuclear translocation. Of interest, specific blockage of the ERK1/2 pathway drastically reduced up-modulation of MSU crystal-mediated chemokine production and activation of nuclear factors. Similarly, selective inhibition of NF-κB suppressed NF-κB DNA binding activity and the induction of all chemokine transcripts. These findings indicate that ERK1/2-dependent signals seem to be required for AP-1 and NF-κB activation and subsequent mRNA expression of the various macrophage chemokines. In addition, transcription and stability assays performed in presence of actinomycin D showed that MSU crystal-mediated MIP-1β mRNA up-regulation resulted solely from transcriptional control, whereas that of MIP-1α, MIP-2, and MCP-1 was due to both gene transcription activation and mRNA posttranscriptional stabilization. Overall, the results of this study help to define the molecular events that govern macrophage chemokine regulation in response to MSU crystals, which is of paramount importance to better understand, and eventually to tame, the inflammatory response during acute gout.

Plasmin-induced expression of cytokines and tissue factor in human monocytes involves AP-1 and IKKβ-mediated NF-κB activation

Blood ◽  
2001 ◽  
Vol 97 (12) ◽  
pp. 3941-3950 ◽  
Author(s):  
Tatiana Syrovets ◽  
Marina Jendrach ◽  
Angela Rohwedder ◽  
Almut Schüle ◽  
Thomas Simmet
Keyword(s):  
Tissue Factor ◽  
Nuclear Translocation ◽  
Lipid Mediator ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Human Monocytes ◽  
Mobility Shift ◽  
Concentration Dependent Manner ◽  
Iκb Kinase ◽  
Tnf Α

It was previously shown that plasmin activates human peripheral monocytes in terms of lipid mediator release and chemotactic migration. Here it is demonstrated that plasmin induces proinflammatory cytokine release and tissue factor (TF) expression by monocytes. Plasmin 0.043 to 1.43 CTA U/mL, but not active site-blocked plasmin, triggered concentration-dependent expression of mRNA for interleukin-1α (IL-1α), IL-1β, tumor necrosis factor-α (TNF-α), and TF with maximum responses after 4 hours. Plasmin-mediated mRNA expression was inhibited in a concentration-dependent manner by the lysine analoguetrans-4-(aminomethyl)cyclohexane-1-carboxylic acid (t-AMCA). Increases in mRNA levels were followed by concentration- and time-dependent release of IL-1α, IL-1β and TNF-α and by TF expression on monocyte surfaces. Neither cytokines nor TF could be detected when monocytes were preincubated with actinomycin D or cycloheximide. Electrophoretic mobility shift assays indicated plasmin-induced activation of NF-κB; DNA-binding complexes were composed of p50, p65, and c-Rel, as shown by supershift experiments. Nuclear translocation of NF-κB/Rel proteins coincided with IκBα degradation. At variance with endotoxic lipopolysaccharide, plasmin elicited the rapid degradation of another cytoplasmic NF-κB inhibitor, p105. Proteolysis of NF-κB inhibitors was apparently due to transient activation of IκB kinase (IKK) β that reached maximum activity at 1 hour after plasmin stimulation. In addition, AP-1 binding was increased in plasmin-treated monocytes, with most complexes composed of JunD, c-Fos, and FosB. These findings further substantiate the role of plasmin as a proinflammatory activator of human monocytes and reveal an important new link between the plasminogen-plasmin system and inflammation.

The Cellular Uptake and Apoptotic Efficiency of Colchicine is Correlated with Downregulation of MMP-9 mRNA Expression in SW480 Colon Cancer Cells

2019 ◽  
Vol 18 (13) ◽  
pp. 1927-1933
Author(s):  
Nuri Ozmen ◽  
Ecem Kaya-Sezginer ◽  
Filiz Bakar-Ates
Keyword(s):  
Mrna Expression ◽  
Hplc Analysis ◽  
Nuclear Translocation ◽  
Apoptotic Cell ◽  
Annexin V ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Anticancer Effects ◽  
Sw480 Cells

Background: Colchicine, a tricyclic alkaloid, is commonly used in treatment due to its antiinflammatory and anti-fibrotic effects. Besides its toxicity at high doses, colchicine is reported for its potential anticancer effects at lower concentrations. The present study aimed to evaluate the anticancer effects of colchicine in SW480 cells. Methods: The effect of colchicine on cell proliferation was determined by MTT assay. The cellular colchicine uptake was measured by HPLC analysis. The apoptotic effects was evaluated by annexin v binding assay and MMP-9 mRNA expression was determined by RT-PCR experiments. Results: Colchicine showed significant cytotoxicity at 10 ng/ml and higher concentrations and caused a cell cycle arrest of SW480 cells at G2/M phase. The results of HPLC analysis showed that colchicine uptake was increased in correlation with treated concentrations. Colchicine concentrations have increased the amount of apoptotic cell population. The elisa and western blot measurements showed that colchicine led to nuclear translocation of NF-κB proteins and increased caspase levels. The real time PCR experiments showed that colchicine has inhibitory effect on MMP-9 mRNA expression in a concentration dependent manner. Conclusion: These results illustrated that low dose colchicine efficiently induced cell death and apoptosis of SW480 cells and the inhibition of MMP-9 mRNA levels was significantly correlated with the amount of cellular colchicine uptake, suggesting that colchicine has a potential value in the treatment of human colorectal cancer.

Sign in / Sign up

Export Citation Format

Share Document