scholarly journals Morin Induces Melanogenesis via Activation of MAPK Signaling Pathways in B16F10 Mouse Melanoma Cells

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2150
Author(s):  
SeoYeon Shin ◽  
JaeYeon Ko ◽  
MinJeong Kim ◽  
Nuri Song ◽  
KyungMok Park
Keyword(s):  
Protein Expression ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Melanoma Cells ◽  
Mapk Signaling ◽  
Tyrosinase Activity ◽  
Melanin Biosynthesis ◽  
Mouse Melanoma ◽  
Melanin Contents ◽  
Mapk Signaling Pathways

Morin is a well-known flavonoid, and has been reported to have various properties, such as anti-cell death, antioxidant, and anti-inflammatory properties. Although studies on the biochemical and biological actions of morin have been reported, the melanin biosynthesis effects and molecular mechanisms are unknown. In this study, we first found that morin has the effect of enhancing melanin biosynthesis in B16F10 mouse melanoma cells, and analyzed the molecular mechanism. In this study, we examined the effects of morin on the melanin contents and tyrosinase activity, as well as the protein expression levels of the melanogenic enzymes TRP-1, TRP-2, and microphtalmia-associated transcription factor (MITF) in B16F10 mouse melanoma cells. Morin showed no cytotoxicity in the concentration range of 5–100 μM, and significantly increased the intracellular tyrosinase activity and melanin contents. In mechanism analysis, morin increased the protein expression of TRP-1, TRP-2, and MITF associated with melanogenesis. Furthermore, morin increased phosphorylated ERK and p38 at the early time, and decreased phosphorylated ERK after 12 h. The results suggest that morin enhances melanin synthesis through the MAPK signaling pathways in B16F10 mouse melanoma cells.

Berberine inhibits lipopolysaccharide-induced expression of inflammatory cytokines by suppressing TLR4-mediated NF-ĸB and MAPK signaling pathways in rumen epithelial cells of Holstein calves

2019 ◽  
Vol 86 (2) ◽  
pp. 171-176 ◽  
Author(s):  
Chenxu Zhao ◽  
Yazhou Wang ◽  
Xue Yuan ◽  
Guoquan Sun ◽  
Bingyu Shen ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Signaling Pathways ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Inflammatory Drug ◽  
Anti Inflammatory ◽  
Mapk Signaling Pathways ◽  
Rumen Epithelial Cells

AbstractSubacute ruminal acidosis (SARA) can increase the level of inflammation and induce rumenitis in dairy cows. Berberine (BBR) is the major active component of Rhizoma Coptidis, which is a type of Chinese anti-inflammatory drug for gastrointestinal diseases. The purpose of this study was to investigate the anti-inflammatory effects of BBR on lipopolysaccharide (LPS)-stimulated rumen epithelial cells (REC) and the underlying molecular mechanisms. REC were cultured and stimulated with LPS in the presence or absence of different concentrations of BBR. The results showed that cell viability was not affected by BBR. Moreover, BBR markedly decreased the concentrations and mRNA expression of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the LPS-treated REC in a dose-dependent manner. Importantly, Western blotting analysis showed that BBR significantly suppressed the protein expression of toll-like receptor 4 (TLR4) and myeloid differentiation primary response protein (MyD88) and the phosphorylation of nuclear factor-κB (NF-κB), inhibitory kappa B (IκBα), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) in LPS-treated REC. Furthermore, the results of immunocytofluorescence showed that BBR significantly inhibited the nuclear translocation of NF-κB p65 induced by LPS treatment. In conclusion, the protective effects of BBR on LPS-induced inflammatory responses in REC may be due to its ability to suppress the TLR4-mediated NF-κB and MAPK signaling pathways. These findings suggest that BBR can be used as an anti-inflammatory drug to treat inflammation induced by SARA.

scholarly journals Hydrangea serrata (Thunb.) Ser. Extract Attenuate UVB-Induced Photoaging through MAPK/AP-1 Inactivation in Human Skin Fibroblasts and Hairless Mice

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 533 ◽  
Author(s):  
Hee-Soo Han ◽  
Ji-Sun Shin ◽  
Da-Bin Myung ◽  
Hye Ahn ◽  
Sun Lee ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Collagen Degradation ◽  
Hot Water ◽  
Mrna Levels ◽  
Skin Damage ◽  
Hairless Mice ◽  
Skin Photoaging ◽  
Mapk Signaling Pathways

Skin photoaging is mainly caused by exposure to ultraviolet (UV) light, which increases expressions of matrix metalloproteinases (MMPs) and destroys collagen fibers, consequently inducing wrinkle formation. Nutritional factors have received scientific attention for use as agents for normal skin functions. The aim of this study was to investigate the effect of hot water extracts from the leaves of Hydrangea serrata (Thunb.) Ser. (WHS) against ultraviolet B (UVB)-induced skin photoaging and to elucidate the underlying molecular mechanisms in human foreskin fibroblasts (Hs68) and HR-1 hairless mice. WHS recovered UVB-reduced cell viability and ameliorated oxidative stress by inhibiting intracellular reactive oxygen species (ROS) generation in Hs68 cells. WHS rescued UVB-induced collagen degradation by suppressing MMP expression, and reduced the mRNA levels of inflammatory cytokines. These anti-photoaging activities of WHS were associated with inhibition of the activator protein 1 (AP-1), signal transduction and activation of transcription 1 (STAT1), and mitogen-activated protein kinase (MAPK) signaling pathways. Oral administration of WHS effectively alleviated dorsal skin from wrinkle formation, epidermal thickening, collagen degradation, and skin dehydration in HR-1 hairless mice exposed to UVB. Notably, WHS suppressed UVB activation of the AP-1 and MAPK signaling pathways in dorsal mouse skin tissues. Taken together, our data indicate that WHS prevents UVB-induced skin damage due to collagen degradation and MMP activation via inactivation of MAPK/AP-1 signaling pathway.

scholarly journals MAPK signaling pathways regulate IL-8 mRNA stability and IL-8 protein expression in cystic fibrosis lung epithelial cell lines

2011 ◽  
Vol 300 (1) ◽  
pp. L81-L87 ◽  
Author(s):  
Sharmistha Bhattacharyya ◽  
Usha Gutti ◽  
Jose Mercado ◽  
Chad Moore ◽  
Harvey B. Pollard ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Protein Expression ◽  
Signaling Pathways ◽  
Mrna Stability ◽  
Mapk Signaling ◽  
Lung Epithelial Cells ◽  
Lung Epithelial ◽  
The Stability ◽  
Mapk Signaling Pathways

Cystic fibrosis (CF) is characterized by a massive proinflammatory phenotype in the lung, caused by mutations in the CFTR gene. IL-8 and other proinflammatory mediators are elevated in the CF airway, and the immediate mechanism may depend on disease-specific stabilization of IL-8 mRNA in CF lung epithelial cells. MAPK signaling pathways impact directly on IL-8 protein expression in CF cells, and we have hypothesized that the mechanism may also involve stabilization of the IL-8 mRNA. To test this hypothesis, we have examined the effects of pharmacological and molecular inhibitors of p38, and downstream MK2, ERK1/2, and JNK, on stability of IL-8 mRNA in CF lung epithelial cells. We previously showed that tristetraprolin (TTP) was constitutively low in CF and that raising TTP destabilized the IL-8 mRNA. We therefore also tested these effects on CF lung epithelial cells stably expressing TTP. TTP binds to AU-rich elements in the 3′-UTR of the IL-8 mRNA. We find that inhibition of p38 and ERK1/2 reduces the stability of IL-8 mRNA in parental CF cells. However, neither intervention further lowers TTP-dependent destabilization of IL-8 mRNA. By contrast, inhibition of the JNK-2 pathway has no effect on IL-8 mRNA stability in parental CF cell, but rather increases the stability of the message in cells expressing high levels of TTP. However, we find that inhibition of ERK1/2 or p38 leads to suppression of the effect of JNK-2 inhibition on IL-8 mRNA stability. These data thus lend support to our hypothesis that constitutive MAPK signaling and proteasomal activity might also contribute, along with aberrantly lower TTP, to the proinflammatory phenotype in CF lung epithelial cells by increasing IL-8 mRNA stability and IL-8 protein expression.

Temozolomide combined with the PI3K inhibitor LY294002 or the mTOR inhibitor rapamycin inhibits melanoma cell growth, survival and invasion

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8559-8559 ◽  
Author(s):  
F. E. Meier ◽  
K. Lasithiotakis ◽  
B. Schittek ◽  
T. Sinnberg ◽  
C. Garbe
Keyword(s):  
Cell Growth ◽  
Metastatic Melanoma ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Mtor Inhibitor ◽  
Melanoma Cells ◽  
Mapk Signaling ◽  
Pi3k Inhibitor ◽  
Mapk Signaling Pathways

8559 Background: Potential therapeutic targets in the treatment of metastatic melanoma have emerged, to which pharmacological inhibitors have been designed, which may enhance tumor chemosensitivity. In melanoma, dacarbazine is considered to be the most effective agent although total responses do not exceed 20% The clinical activity of temozolomide is similar to that of dacarbazine, but temozolomide has the advantages of being absorbed orally and of crossing the blood-brain barrier. Many clinical trials of targeted therapy and chemotherapy combinations lack rigorous preclinical evaluation and may neglect relevant mechanistic interactions. The PI3K-AKT-mTOR (AKT) and RAS-RAF- MEK-ERK (MAPK) signaling pathways are constitutively activated in melanoma, and appear to play a role in chemoresistance. Methods: In this study, a panel of pharmacological inhibitors was utilized in order to block the AKT and MAPK signaling pathways at different levels (AKT: PI3K, mTOR; MAPK: RAF, MEK) in 5 human metastatic melanoma cell lines. The effects on chemosensitivity to temozolomide and cisplatin was then investigated. Results: The effects of most inhibitors on chemosensitivity varied significantly between the different cell lines. However, LY294002, a PI3K inhibitor and rapamycin, an mTOR inhibitor, consistently enhanced chemosensitivity. Treatment of melanoma cells with temozolomide or cisplatin combined with LY294002 or rapamycin had a strong effect on melanoma cell growth and survival. Invasive melanoma growth in organotypic cultures of human skin was suppressed completely. The most pronounced potentiation of efficacy was seen with temozolomide in combination with rapamycin. Conclusions: These data suggest that LY294002 and rapamycin can render melanoma cells susceptible to apoptosis, induced by chemotherapeutic agents such as temozolomide and cisplatin. Since both temozolomide and rapamycin are used clinically, the combination of temozolomide with rapamycin might potentially be utilized as an approach in melanoma treatment. This combination merits clinical investigation. No significant financial relationships to disclose.

scholarly journals Hypoxia Activates Notch4 via ERK/JNK/P38 MAPK Signaling Pathways to Promote Lung Adenocarcinoma Progression and Metastasis

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaochen Li ◽  
Xiaopei Cao ◽  
Hanqiu Zhao ◽  
Mingzhou Guo ◽  
Xiaoyu Fang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Signaling Pathways ◽  
P38 Mapk ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Binding Interaction ◽  
Lung Cancer Patients ◽  
Cell Progression ◽  
Mapk Signaling Pathways

Hypoxia contributes to the progression and metastasis of lung adenocarcinoma (LUAD). However, the specific underlying molecular mechanisms have not been fully elucidated. Here we report that Notch4 is upregulated in lung tissue from lung cancer patients. Functionally, Hypoxia activates the expressions of Delta-like 4 and Notch4, resulting in the excessive proliferation and migration of LUAD cells as well as apoptotic resistance. Notch4 silencing reduced ERK, JNK, and P38 activation. Meanwhile, Notch4 overexpression enhanced ERK, JNK, and P38 activation in LUAD cells. Furthermore, Notch4 exerted pro-proliferation, anti-apoptosis and pro-migration effects on LUAD cells that were partly reversed by the inhibitors of ERK, JNK, and p38. The binding interaction between Notch4 and ERK/JNK/P38 were confirmed by the co-immunoprecipitation assay. In vivo study revealed that Notch4 played a key role in the growth and metastasis of LUAD using two xenograft models. This study demonstrates that hypoxia activates Notch4-ERK/JNK/P38 MAPK signaling pathways to promote LUAD cell progression and metastasis.

scholarly journals UTRN inhibits melanoma growth by suppressing p38 and JNK/c-Jun signaling pathways

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sitong Zhou ◽  
Wen Ouyang ◽  
Xi Zhang ◽  
Lexi Liao ◽  
Xiaobing Pi ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Melanoma Cells ◽  
Mapk Signaling ◽  
Cell Counting ◽  
Clinical Samples ◽  
Control Group ◽  
Proliferation Ability ◽  
Melanoma Growth

Abstract Background Utrophin (UTRN), as a tumor suppressor gene, is involved in various cancer progression. The function of UTRN in the melanoma process and the related molecular mechanisms are still unclear. Herein, we studied the function of UTRN in melanoma growth and the relevant molecular mechanisms. Methods Using the GEO database and UCSC Xena project, we compared the expression of UTRN in non-cancerous and melanoma tissues. Immunohistochemistry (IHC) staining, qRT-PCR and Western Blot (WB) were performed to evaluate UTRN expression in clinical samples. A total of 447 cases with UTRN expression data, patient characteristics and survival data were extracted from TCGA database and analyzed. After stable transduction and single cell cloning, the proliferation ability of A375 human melanoma cells was analyzed by Cell Counting Kit‑8 (CCK) and 5‑ethynyl‑2′‑deoxyuridine (EdU) incorporation assays. GSEA was performed to predict the mechanism by which UTRN regulated melanoma growth. Then WB analysis was used to assess the protein expression levels of pathway signaling in overexpression (EXP) melanoma cells. Epac activator 8-pCPT-2′-O-Me-cAMP was then used to evaluate the proliferation ability by activation of p38 and JNK/c-Jun signaling pathways. Results Data from GEO and UCSC Xena project indicated that UTRN expression was decreased in melanoma. Experiment on clinical samples further confirmed our finding. TCGA results showed that a reduced expression of UTRN in 447 melanoma samples was associated with advanced clinical characteristics (T stage, Clark level, ulceration), shorter survival time and poorer prognosis. In addition, up-regulated UTRN expression inhibited melanoma cell proliferation when compared to control group. MAPK signaling pathway was presented in both KEGG and BioCarta databases by using GSEA tool. WB results confirmed the down-regulated expression of p38, JNK1 and c-Jun in EXP group when compared to control group. Epac activator 8-pCPT-2′-O-Me-cAMP treatment could partially rescue proliferation of tumor cells. Conclusion We have demonstrated that reduced UTRN predicted poorer prognosis and UTRN inhibited melanoma growth via p38 and JNK1/c-Jun pathways. Therefore, UTRN could serve as a tumor suppressor and novel prognostic biomarker for melanoma patients.

scholarly journals Frutescone O from Baeckea frutescens Blocked TLR4-Mediated Myd88/NF-κB and MAPK Signaling Pathways in LPS Induced RAW264.7 Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaobing Lin ◽  
Junhan Zhang ◽  
Decai Fan ◽  
Jiqin Hou ◽  
Hao Wang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Raw264.7 Cells ◽  
Raw264.7 Macrophages ◽  
Anti Inflammatory ◽  
Baeckea Frutescens ◽  
Myd88 Signaling ◽  
Myeloid Differentiation Factor ◽  
Mapk Signaling Pathways

Frutescone O was isolated from the aerial parts of Baeckea frutescens L., which was commonly used as a folk medicinal material for treating anti-inflammatory disease in South East Asia. This study aimed to investigate the anti-inflammatory activity and related signaling cascade of Frutescone O (Fru) in LPS induced RAW264.7 cells. The anti-inflammation activity of Frutescone O was determined according to the inhibitory effects on the secretion of nitric oxide (NO), expression of inducible NO synthase, and pro-inflammatory cytokines. The regulation of Myeloid differentiation factor 88 (Myd88), inhibition of NF-κB, and MAPK pathways were further investigated for molecular mechanisms. Fru significantly decreased the expression of iNOS and the production of NO in LPS-stimulated RAW264.7 cells. It also dose-dependently suppressed LPS induced expression of IL-1β, IL-6, and TNF-α. Furthermore, Fru remarkably inhibited the upregulation of NF-κB (p50) expression in the nucleus and the phosphorylation ratio of p38, JNK, ERK, and Myd88 signaling protein. The molecular docking and cellular thermal shift assay (CETSA) results indicated that Fru participated in a robust and stable interaction with the active site of TLR4-MD2. Thus, Fru suppressed the LPS induced inflammation in RAW264.7 cells by blocking the TLR4 mediated signal transduction through the NF-κB and MAPK signaling pathways and inhibiting the Myd88 and iNOS expression.

scholarly journals Computational and In Vitro Analysis of Plumbagin’s Molecular Mechanism for the Treatment of Hepatocellular Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Yanfei Wei ◽  
Yuning Lin ◽  
Wanjun Chen ◽  
Shasha Liu ◽  
Lijie Jin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Anticancer Properties ◽  
Vitro Analysis ◽  
Mapk Signaling Pathways

Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor and the second leading cause of cancer-related death in the world. Plumbagin (PL) is a small molecule naphthoquinone compound isolated from Plumbago zeylanica L. that has important anticancer properties, but its mechanism requires further investigation. In this study, we used a comprehensive network pharmacology approach to study the mechanism of action of PL for the treatment of HCC. The method includes the construction of multiple networks; moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify biological processes and signaling pathways. Subsequently, in vitro experiments were performed to verify the predicted molecular mechanisms obtained from the network pharmacology-based analysis. Network pharmacological analysis showed that PL may exert anti-HCC effects by enhancing reactive oxygen species (ROS) production to generate oxidative stress and by regulating the PI3K/Akt and MAPK signaling pathways. In vitro experiments confirmed that PL mainly mediates the production of ROS, regulates the PI3K/Akt and MAPK signaling pathways to promote apoptosis and autophagy, and shows significant therapeutic effects on HCC. In conclusion, our work proposes a comprehensive systems pharmacology approach to explore the potential mechanism of PL for the treatment of HCC.

scholarly journals Ethyl Acetate Extract of Asclepias curassavica Induced Apoptosis in Human Cancer Cells via Activating p38 and JNK MAPK Signaling Pathways

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Xi Zheng ◽  
Ying Xu ◽  
Bei Liu ◽  
Yan Qi ◽  
Ying Zhang ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Signaling Pathways ◽  
Antitumor Effect ◽  
Molecular Mechanisms ◽  
Ethyl Acetate Extract ◽  
Mapk Signaling ◽  
Asclepias Curassavica ◽  
Induced Apoptosis ◽  
Mapk Signaling Pathways

Background. Asclepias curassavica L. (Asclepiadaceae), as a traditional medicinal plant, is used as treatment for tumors in traditional Chinese and Indian medical practice. However, its underlying molecular mechanisms remain largely unresolved. The current study investigated its antitumor activity and the underlying molecular mechanisms. Method. Cell viability was detected by a real-time cell analysis system and MTT assay. Antitumor effect of ethyl acetate extract of Asclepias curassavica (EAAC) on NIC-H1975 tumors in vivo was assessed in BALB/c-nu/nu mouse. Apoptosis was measured using Hoechst33342 staining and Annexin V/PI-staining. Apoptosis-related proteins and MAPK signaling pathways were analyzed based on Western blot assay. Results. EAAC exhibited the highest cytotoxic activity in vitro than other polar parts. Meanwhile, EAAC could inhibit sensitive cell line NIC-H1975 proliferation in a concentration-dependent and time-dependent manner. Furthermore, EAAC had a significant inhibitory effect on NIC-H1975 tumor growth in BALB/c-nu/nu mouse. NIC-H1975 cells showed obvious apoptosis characteristics after EAAC treatment. Fas, caspase family members caspase 3, caspase 9, and caspase 8 showed dose-dependent induction by EAAC treatment, with increasing PARP cleavage. Additionally, EAAC significantly downregulated antiapoptotic proteins Bcl-2, XIAP, survivin, and Mcl-1 and upregulated proapoptosis proteins Bak, Bax, as well as activation of p38 and JNK MAPK signaling pathways. Moreover, inhibiting p38 and JNK MAPK by pharmacological inhibitors abrogated EAAC-induced apoptosis. Conclusion. Our data indicated that EAAC exerted potent antitumor effect both in vitro and in vivo by triggering the apoptotic pathway.

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