scholarly journals Oxyresveratrol Inhibits TNF-α-Stimulated Cell Proliferation in Human Immortalized Keratinocytes (HaCaT) by Suppressing AKT Activation

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 63
Author(s):  
Nitwara Wikan ◽  
Phateep Hankittichai ◽  
Phatarawat Thaklaewphan ◽  
Saranyapin Potikanond ◽  
Wutigri Nimlamool
Keyword(s):  
Akt Pathway ◽  
Functional Assay ◽  
Dependent Manner ◽  
Induce Cell Cycle Arrest ◽  
Ki 67 ◽  
Akt Phosphorylation ◽  
Akt Activation ◽  
Cycle Arrest ◽  
Tnf Α ◽  
Psoriasis Therapy

Psoriasis is a complex inflammatory disease characterized by hyperproliferative keratinocyte caused by active PI3K/AKT signaling. TNF-α concentrated in the psoriatic lesions stimulates AKT activation. We previously discovered that oxyresveratrol inhibited inflammation via suppressing AKT phosphorylation, therefore oxyresveratrol may possess a conserved property to block AKT activation and proliferation in keratinocyte in response to TNF-α. Our current study proved that oxyresveratrol exhibited potent anti-proliferative effects against TNF-α. These effects are explained by the findings that oxyresveratrol could potentially inhibit TNF-α-stimulated AKT and GSK3-β activation in a dose-dependent manner, and its inhibitory pattern was comparable to that of a specific PI3K inhibitor. Results from immunofluorescence supported that oxyresveratrol effectively inhibited AKT and GSK3-β activation in individual cells upon TNF-α stimulation. Furthermore, functional assay confirmed that oxyresveratrol repressed the expansion of the HaCaT colony over 3 days, and this was caused by the ability of oxyresveratrol to induce cell cycle arrest at S and G2/M phases and the reduction in the expression of a proliferative marker (Ki-67) and a survival marker (MCL-1). Given the importance of TNF-α and the PI3K/AKT pathway in the psoriatic phenotype, we anticipate that oxyresveratrol, which targets the TNF-α-stimulated PI3K/AKT pathway, would represent a promising psoriasis therapy in the near future.

H2O2-induced transactivation of EGF receptor requires Src and mediates ERK1/2, but not Akt, activation in renal cells

2004 ◽  
Vol 286 (5) ◽  
pp. F858-F865 ◽  
Author(s):  
Shougang Zhougang ◽  
Rick G. Schnellmann
Keyword(s):  
Oxidative Stress ◽  
Egf Receptor ◽  
Primary Cultures ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
Dependent Manner ◽  
Egfr Transactivation ◽  
Akt Phosphorylation ◽  
Akt Activation ◽  
Renal Proximal Tubular Cells

Although oxidative stress activates epidermal growth factor receptor (EGFR), ERK1/2, and Akt in a number of cell types, the mechanisms by which oxidative stress activates these kinases are not well defined in renal epithelial cells. Exposure of primary cultures of rabbit renal proximal tubular cells to hydrogen peroxide (H2O2) stimulated Src, EGFR, ERK1/2, and Akt activation in a time-dependent manner as determined by the phosphorylation of each protein. The Src inhibitor PP1 completely blocked EGFR, ERK1/2, and Akt phosphorylation following H2O2 exposure. In contrast, blockade of the EGFR by AG1478 inhibited phosphorylation of ERK1/2 but not Src or Akt phosphorylation following H2O2 exposure. Exogenous EGF stimulated EGFR, ERK1/2, and Akt activation and the EGFR inhibitor blocked phorphorylation of ERK1/2 and Akt. The presence of PP1, but not AG1478, significantly accelerated H2O2-induced cell death. These results suggest that Src mediates H2O2-induced EGFR transactivation. H2O2- and EGF-induced ERK1/2 activation is mediated by EGFR, whereas Akt is activated by Src independent of EGFR following H2O2 exposure. Src-mediated EGFR transactivation contributes to a survival response following oxidative injury.

Abstract 323: A Peptide Inhibitor of PTEN Improves Mouse Survival After Cardiac Arrest

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Xiangdong Zhu ◽  
Jing Li ◽  
Huashan Wang ◽  
Chunpei Lee ◽  
Zhiyi Zhu ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Mouse Model ◽  
Glucose Utilization ◽  
Polyol Pathway ◽  
Treated Group ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Akt Phosphorylation ◽  
Akt Activation

Introduction: Prior works from our laboratory found that cooling protection after cardiac arrest is mediated by enhanced Akt activation and in cardiomyocyte the cooling protection can be reproduced using PTEN chemical inhibitor. The current study extend these works by designing a cell-permeable peptide, TAT-PTEN9c, which is more specific for PTEN. Hypothesis: We hypothesized that TAT-PTEN9c interferes with endogenous PTEN binding to cell membrane adaptor resulting in increased Akt activation, enhanced glucose utilization and improved mouse survival after cardiac arrest. Methods: Mouse cardiomyocytes were isolated from 1-3 day old mouse pups. Western blot was used to determine the efficacy of TAT-PTEN9c for Akt activation. The effect of TAT-PTEN9c on mouse survival after cardiac arrest was determined in a mouse model. TAT-PTEN9c (7.5 mg/kg) was given intravenously (IV) after CPR. As a measure of impaired glucose utilization, sorbitol content in heart and brain was determined by a fluorescence assay of NADH formation using sorbitol dehydrogenase and NAD + . Results: TAT-PTEN9c peptide enhanced Akt activation in mouse cardiomyocytes in a concentration-dependent manner. Akt phosphorylation was observed at 1 μM and further increased with 10 μM TAT-PTEN9c. TAT-PTEN9c blocked the binding of endogenous PTEN to MAGI2 in a co-immunoprecipitation assay, while TAT-PTEN3a control had no inhibitory effect. In a mouse model of cardiac arrest, survival was significantly increased in the TAT-PTEN9c treated group compared to saline controls at 4 h (10/15, 67% vs. 6/15, 40%, P < 0.05) after CPR. TAT-PTEN9c improved MAP at both R30 min and R2h. The treated mice had increased Akt phosphorylation at R15 min in both heart and brain tissues with significantly decreased sorbitol content and reduced release of taurine and glutamate into blood, suggesting improved metabolic recovery and glucose utilization. Conclusion: TAT-PTEN9c can be used after CPR in a mouse SCA model to rapidly enhance Akt activation and decrease glucose shunting to the polyol pathway in critical organs, preventing osmotic injury and early cardiovascular collapse and death.

scholarly journals Extracellular Vesicles from Adipose-Derived Mesenchymal Stem/Stromal Cells Accelerate Migration and Activate AKT Pathway in Human Keratinocytes and Fibroblasts Independently of miR-205 Activity

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Andrea da Fonseca Ferreira ◽  
Pricila da Silva Cunha ◽  
Virgínia Mendes Carregal ◽  
Priscila de Cássia da Silva ◽  
Marcelo Coutinho de Miranda ◽  
...  
Keyword(s):  
Wound Healing ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Average Diameter ◽  
Skin Wound ◽  
Akt Pathway ◽  
Skin Wound Healing ◽  
Akt Phosphorylation ◽  
Akt Activation

Mesenchymal stem/stromal cells (MSCs) are promising tools in cell therapy. They secrete extracellular vesicles (EVs) that carry different classes of molecules that can promote skin repair, but the mechanisms are poorly understood. Skin wound healing is a complex process that requires the activity of several signaling pathways and cell types, including keratinocytes and fibroblasts. In this study, we explored whether adipose tissue MSC-derived EVs could accelerate migration and proliferation of keratinocytes and fibroblasts, activate the AKT pathway, and promote wound healing in vivo. Furthermore, we evaluated if EV effects are miR-205 dependent. We found that MSC EVs had an average diameter of 135 nm. Keratinocytes and fibroblasts exposed to EVs exhibited higher levels of proliferation, migration, and AKT activation. Topical administration of EVs accelerated skin wound closure. Knockdown of miR-205 decreased AKT phosphorylation in fibroblasts and keratinocytes, whereas migration was decreased only in keratinocytes. Moreover, knockdown of miR-205 failed to inhibit AKT phosphorylation in fibroblasts and keratinocytes exposed to EVs. About the mechanism of EV effects, we found that incubation with EVs prevented inhibition of AKT activation by miR-205 knockdown, suggesting that EVs activate AKT independently of miR-205. In conclusion, we demonstrated that EVs are a promising tool for wound healing.

scholarly journals The PI3K/Akt pathway is involved in early infection of some exogenous avian leukosis viruses

2011 ◽  
Vol 92 (7) ◽  
pp. 1688-1697 ◽  
Author(s):  
Shao-zhen Feng ◽  
Wei-sheng Cao ◽  
Ming Liao
Keyword(s):  
Viral Entry ◽  
Early Stage ◽  
Dependent Manner ◽  
Phosphatidylinositol 3 Kinase ◽  
Akt Phosphorylation ◽  
Akt Activation ◽  
Pi3k Inhibitors ◽  
Cellular Factors ◽  
Dose Dependent

Avian leukosis virus (ALV) is an enveloped and oncogenic retrovirus. Avian leukosis caused by the members of ALV subgroups A, B and J has become one of the major problems challenging the poultry industry in China. However, the cellular factors such as signal transduction pathways involved in ALV infection are not well defined. In this study, our data demonstrated that ALV-J strain NX0101 infection in primary chicken embryo fibroblasts or DF-1 cells was correlated with the activity and phosphorylation of Akt. Akt activation was initiated at a very early stage of infection independently of NX0101 replication. The specific phosphatidylinositol 3-kinase (PI3K) inhibitors LY294002 or wortmannin could suppress Akt phosphorylation, indicating that NX0101-induced Akt phosphorylation is PI3K-dependent. ALV-A strain GD08 or ALV-B strain CD08 infection also demonstrated a similar profile of PI3K/Akt activation. Treatment of DF-1 cells with the drug 5-(N, N-hexamethylene) amiloride that inhibits the activity of chicken Na+/H+ exchanger type 1 significantly reduced Akt activation induced by NX0101, but not by GD08 and CD08. Akt activation triggered by GD08 or CD08 was abolished by clathrin-mediated endocytosis inhibitor chlorpromazine. Receptor-mediated endocytosis inhibitor dansylcadaverine had a negligible effect on all ALV-induced Akt phosphorylation. Moreover, viral replication of ALV was suppressed by LY294002 in a dose-dependent manner, which was due to the inhibition of virus infection by LY294002. These data suggest that the activation of the PI3K/Akt signalling pathway by exogenous ALV infection plays an important role in viral entry, yet the precise mechanism remains under further investigation.

scholarly journals Suppression of Sirtuin-1 Increases IL-6 Expression by Activation of the Akt Pathway During Allergic Asthma

2017 ◽  
Vol 43 (5) ◽  
pp. 1950-1960 ◽  
Author(s):  
Lingling Tang ◽  
Qingge Chen ◽  
Ziyu Meng ◽  
Li Sun ◽  
Linyun Zhu ◽  
...  
Keyword(s):  
Allergic Asthma ◽  
Sirtuin 1 ◽  
Akt Pathway ◽  
Epithelial Cell Line ◽  
Dependent Manner ◽  
Airway Epithelial ◽  
Mice Model ◽  
Akt Inhibitor ◽  
Akt Phosphorylation ◽  
Protein Levels

Background/Aims: A growing number of studies have demonstrated that the activity and expression level of sirtuin-1 (SIRT1) are decreased in asthma patients; however, the mechanisms underlying decreased SIRT1 expression and function are still not completely understood. Interleukin (IL)-6 plays important roles in inflammation during allergic asthma. In this study, we examined whether loss of SIRT1 activity regulated the expression of IL-6 and further verified the underlying mechanisms. Methods: The human airway epithelial cell line 16HBE was used to test the effects of the SIRT1 inhibitor (salermide) on expression of IL-6. IL-6 mRNA and protein expression were assessed with real-time polymerase chain reaction (PCR), immunochemistry, and ELISA. OVA-challenged mice were used as an asthma model to investigate the effect of SIRT1 activation on IL-6 and relative Akt phosphorylation level. Results: We found that inhibition of SIRT1 increased IL-6 mRNA and protein levels in a time-dependent manner, which was accompanied by increased Akt pathway activation in 16HBE cells. Furthermore activation of Akt showed upregulated expression of the IL-6 protein whereas Akt inhibitor, LY294002 or Akt siRNA significantly inhibited SIRT1-regulated IL-6 expression. Conversely, activation of SIRT1 inhibited Akt activation and IL-6 expression in an asthmatic mice model and 16HBE cells. Conclusion: Our results indicate the potential role of SIRT1 in regulating inflammation by modulation of IL-6 expression in an Akt-dependent manner during allergic asthma.

TNF-α induces MMP-9 expression via activation of Src/EGFR, PDGFR/PI3K/Akt cascade and promotion of NF-κB/p300 binding in human tracheal smooth muscle cells

2007 ◽  
Vol 292 (3) ◽  
pp. L799-L812 ◽  
Author(s):  
Chiang-Wen Lee ◽  
Chih-Chung Lin ◽  
Wei-Ning Lin ◽  
Kao-Chih Liang ◽  
Shue-Feng Luo ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Growth Factor Receptors ◽  
Tracheal Smooth Muscle ◽  
Dependent Manner ◽  
Akt Phosphorylation ◽  
Tnf Α ◽  
Phosphorylated Akt

TNF-α has been shown to induce matrix metalloproteinase-9 (MMP-9) expression, which, in turn, degrades extracellular matrix in the inflammatory responses. However, the inductive mechanisms of the MMP-9 by TNF-α remain unclear. In human tracheal smooth muscle cells, TNF-α induced MMP-9 expression and Akt phosphorylation in a time-dependent manner, which was attenuated by the inhibitors of Src (PP1), epidermal growth factor receptor (AG1478), PDGFR (AG1296), and PI3K (LY294002), respectively, revealed by reporter gene assay, RT-PCR, zymographic, and Western blot analyses. Transfection with the dominant negative mutants of c-Src (KM, K295M [kinase inactive mutant]), p85, and Akt (KA, K179A) also reduced MMP-9 expression. These findings indicated that MMP-9 expression was regulated by PI3K/Akt via the transactivation of growth factor receptors. Furthermore, LY294002 or wortmannin inhibited Akt phosphorylation but had no effect on NF-κB translocation, which was blocked by helenalin. Mutated NF-κB DNA binding element in the MMP-9 promoter and helenalin also attenuated MMP-9 expression, suggesting that PI3K/Akt and NF-κB independently regulated MMP-9 expression. To support this notion, immunofluorescence staining and immunoprecipitation were applied to characterize the transcription factors involved in these responses. The results showed that LY294002 and curcumin blocked Akt translocation into nucleus. In contrast, p300, acetyl-histone (H3), and NF-κB p65 were found to be coimmunoprecipitated with the phosphorylated Akt, indicating that these components associated with the MMP-9 promoter are revealed by chromatin immunoprecipitation assay. Thus, our study provides a new insight into the molecular mechanisms that TNF-α-stimulated Akt phosphorylation mediated through transactivation of Src and growth factor receptors may stimulate the recruitment of p300, assemble transcription factor (p65), and then lead to MMP-9 expression.

scholarly journals Ginsenoside Rg2 Attenuates Doxorubicin-induced Cardiomyocyte Apoptosis via PI3K/Akt Pathway

2021 ◽  
Author(s):  
Boyong Qiu ◽  
Meijiao Mao ◽  
Shuai Zhang ◽  
Bing Deng ◽  
Lin Shen ◽  
...  
Keyword(s):  
Cardiomyocyte Apoptosis ◽  
Cell Counting ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Akt Pathway ◽  
Dependent Manner ◽  
P53 Expression ◽  
Akt Phosphorylation ◽  
Underlying Mechanisms ◽  
Dose Dependent ◽  
Important Drug

Abstract Doxorubicin (DOX) is an important drug for cancer therapy; however, its use is limited by its cardiotoxicity. Ginsenoside Rg2 is extracted from Panax ginseng, which is believed to have cardioprotective properties. However, to date, there have been no reports on whether ginsenoside Rg2 could protect cardiomyocytes against DOX. In this study, we investigated the action and underlying mechanisms of ginsenoside Rg2 upon DOX treatment. This study aimed to explore the cardioprotective effects of ginsenoside Rg2 against DOX treatment. Cell Counting kit-8 was used to determine cell viability and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining was used to detect apoptotic cells. Western blotting was used to investigate the relevant pathways. LY294002 (LY294), a PI3K inhibitor, was used in this study. We found that ginsenoside Rg2 significantly (P < 0.01) neutralized cardiomyocyte apoptosis induced by DOX in a dose-dependent manner, which was blocked by LY294. Moreover, ginsenoside Rg2 upregulated Akt phosphorylation through the PI3K/Akt pathway and inhibited p53 expression. Taken together, Ginsenoside Rg2 attenuates DOX-induced cardiomyocyte apoptosis via the PI3K/Akt pathway.

Chronic Lymphocytic Leukemia B-Cells Lack or Express Markedly Reduced Levels of the Phosphatase PHLPP, Which Regulates B-Cell Receptor Induced AKT Activation.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2080-2080
Author(s):  
Mirza Suljagic ◽  
Luca Laurenti ◽  
Muhammad Alam ◽  
Pablo G Longo ◽  
Sami N Malek ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Lines ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Akt Pathway ◽  
Immunoblotting Analysis ◽  
Akt Phosphorylation ◽  
Akt Activation

Abstract The PI3K/AKT pathway plays a central role in regulating cellular growth and survival. This pathway is activated by signals derived from various receptors and is tightly regulated through the action of several phosphatases, including SHIP and PTEN, which hydrolyze the PI3K product PIP3, and the recently identified PHLPP, which directly dephosphorylates AKT. Hyperactivation of the PI3K/AKT pathway has been implicated in the pathogenesis of many types of cancer, including chronic lymphocytic leukemia (CLL) and B-cell lymphoma. In addition, gene expression profiling and real-time RT/PCR analysis have recently shown differential expression of PHLPP mRNA in CLL subsets classified according to the presence of the 13q14 abnormality, with many CLL cases demonstrating absent PHLPP expression altogether. These findings prompted us to compare the levels of PHLPP expression in primary CLL B-cells (n=17) with normal tonsillar B-cells (n=4) and various lymphoma cell lines, including the diffuse large B-cell lymphomas (DLBCL) DHL-4, DHL-6, DHL-8, DHL-10, WSU, Toledo, Ly1, Ly3, Ly7 and Ly18, the Burkitt’s lymphoma BJAB and the prolymphocytic leukemia MEC1. Immunoblotting analysis revealed abundant and uniform expression of PHLPP in normal B-cells and in 7 out of 12 investigated lymphoma cell lines. Higher levels were observed in the BJAB, Ly1 and Ly18 cell lines, whereas PHLPP was undetectable in the DLBCL cell lines WSU and Toledo. Remarkably, PHLPP was either not expressed or was expressed at markedly reduced levels in all of the investigated CLL samples, with levels of expression ranging from 0 to 10% of the levels in normal B-cells. In contrast, the levels of expression of the phosphatase SHIP were relatively similar between CLL and normal B-cells. To determine what are the consequences of reduced PHLPP expression on signaling through AKT in malignant B-lymphocytes, we downregulated PHLPP in BJAB and DHL-4 cells by RNA interference. A significant reduction in the levels of PHLPP was achieved in both cell lines, which amounted to 20–40% of the levels in cells transfected with the control siRNA. Immunoblotting analysis of protein extracts from cells transfected with PHLPP and control siRNA did not show a difference in AKT phosphorylation on Ser473 and Thr308, indicating that a reduction in PHLPP expression is not sufficient to augment basal AKT activity. To determine the effects of PHLPP downregulation on agonist-induced AKT activation, we investigated phosphorylation on Ser473 and Thr308 in BJAB and DHL-4 cells stimulated through the B-cell receptor. In both cell lines downregulation of PHLPP resulted in more than a 50% increase in BCR-induced AKT phosphorylation. In contrast, phosphorylation of other signaling molecules that are also activated by BCR crosslinking, such as PLCγ2 and ERK, appeared unaffected by PHLPP downregulation. These data confirm the functional relevance of PHLPP in AKT regulation in B-lymphoid cells and implicate reduced or absent PHLPP expression in CLL B-cells as a potential determinant of BCR-induced AKT signaling in CLL.

PTEN Regulates SYK-Directed AKT Activation in MCL.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2941-2941
Author(s):  
Martina Rudelius ◽  
Stefania Pittaluga ◽  
Denise Sebasigari ◽  
Theresa Davies-Hill ◽  
Margit Klier ◽  
...  
Keyword(s):  
Cell Lines ◽  
Conflicts Of Interest ◽  
Akt Pathway ◽  
Akt Phosphorylation ◽  
Akt Activation ◽  
Constitutive Activation ◽  
Survival Pathways ◽  
Mantle Cell ◽  
Constitutively Active

Abstract Abstract 2941 Poster Board II-917 Mantle cell lymphoma (MCL) can be divided into two clinicopathologic subtypes, a common or “typical” form, and an aggressive “blastoid” variant. A subset of MCL, including all of the aggressive blastoid variants, shows constitutive activation of the PI3K/AKT pathway. Since the BCR-associated SYK tyrosine kinase can activate the PI3K/AKT pathway during normal BCR signaling, we wished to assess its role in MCL. Five MCL cell lines (Granta 519, Rec-1, Jeko, Z138C and JVM-2) and 32 primary cases were studied for SYK activation and phosphorylation of several SYK targets, including blnk and PLC-gamma. The functional role of SYK was assessed by pharmacologic inhibition with R406, Piceatannol and SYK II inhibitor (2-(2-Aminoethylamino)-4-(3-trifluoromethyl-anilino)-pyrimidine-5-carboxamide, Dihydrochloride, Dihydrate). To rule out off target effects functional data was validated by siRNA experiments. Subsequently we analysed the effects of PTEN and constitutively active (S380A) PTEN in 2 cell lines (Granta 519 and Z138C). All cell lines were found to have constitutively activated SYK accompanied by phosphorylation of its downstream targets blnk and PLC-gamma. Inhibition of SYK with pharmacologic inhibitors or by specific siRNA resulted in AKT inactivation, suggesting a causal relationship between SYK activation and AKT activation in the cell lines. However, all primary MCL cases demonstrated constitutive activation of SYK, regardless of the activation state of AKT. Interestingly, p-AKT expression correlated with PTEN inactivation, as assessed by p-PTEN expression, in both primary cases and MCL cell lines. Increasing PTEN phosphatase activity, by introducing a constitutively active PTEN, abrogated AKT phosphorylation, without affecting SYK activity. These data suggest that SYK activity in MCL is necessary, but not sufficient to activate the PI3K/AKT pathway, and that an additional critical step is the inactivation of PTEN. This study reveals new complexity in the dysregulation of survival pathways in MCL that may be relevant to pathogenesis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals MDA-19 suppresses progression of melanoma via inhibiting the PI3K/Akt pathway

Open Medicine ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. 416-424 ◽  
Author(s):  
Ningning Dang ◽  
Xianguang Meng ◽  
Shanshan Ma ◽  
Qian Zhang ◽  
XiYa Sun ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Melanoma Cells ◽  
Mitochondrial Pathway ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Akt Phosphorylation ◽  
Cancer Agent ◽  
Related Proteins

AbstractObjectiveTo investigate the effect of MDA-19 on progression of melanoma, and explore the relevant mechanism.MethodsThe melanoma cell lines, M14 and UACC257, were treated with different concentrations of MDA-19, then CCK8, clone formation assay, Transwell and flow cytometry assays were performed to examine cell proliferation, migration, invasion and apoptosis, respectively. The expression of apoptosis-related proteins (Bcl-2, Bax and caspase 3 P17), EMT and signaling pathway-related proteins were also detected by Western blot.ResultsMDA-19 inhibited melanoma cells in a dose-dependent manner. Compared to the NC group, MDA-19 significantly inhibited cell growth capacity, migration and invasion of M14 and UACC257 cells, and accelerated cell apoptosis in a mitochondrial pathway through regulating Bcl-2/Bax and Caspase 3 in M14 and UACC257 cells. Moreover, MDA-19 was observed to up-regulate the expression of E-cad and down-regulate the expression of N-cad, Vimentin and Slug in melanoma cells in vitro. Furthermore, MDA-19 could inhibit the PI3K/Akt pathway by blocking Akt phosphorylation (p-Akt) and downstream proteins, P70 and Cyclin D1 in M14 and UACC257 cells.ConclusionOur data demonstrate that MDA-19 could inhibit progression of melanoma by suppressing the PI3K/Akt pathway, suggesting that MDA-19 is a potential anti-cancer agent for therapy of melanoma.

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