scholarly journals Puerarin Induces Hepatocellular Carcinoma Cell Apoptosis Modulated by MAPK Signaling Pathways in a Dose-dependent Manner

2017 ◽  
Vol 37 (8) ◽  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathways ◽  
Cell Apoptosis ◽  
Carcinoma Cell ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Hepatocellular Carcinoma Cell ◽  
Dose Dependent ◽  
Mapk Signaling Pathways

Urocortins exhibit differential effects on PGE2 and PGF2α output via CRHR2 in human myometrium

Reproduction ◽  
2021 ◽  
Author(s):  
Xingji You ◽  
Zixi Chen ◽  
Qianqian Sun ◽  
Ruojing Yao ◽  
Hang Gu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Mapk Signaling ◽  
Human Myometrium ◽  
Dependent Manner ◽  
Camp Production ◽  
Inflammatory Stimuli ◽  
Crh Receptor Type 1 ◽  
Dose Dependent ◽  
Mapk Signaling Pathways

Urocortins (UCNs), belonging to corticotropin-releasing hormone (CRH) family, exert their function via CRH receptor type 1(CRHR1) and 2 (CRHR2). Our previous studies have demonstrated that CRH acts on CRHR1 to potentiate prostaglandin (PG) output induced by inflammatory stimuli in myometrial cells. In the present study, we sought to investigate the effects of UCNs on prostaglandin (PG) output via CRHR2 in cultured human uterine smooth muscle cells (HUSMCs) from human term myometrium. We found that UCN and UCN3 treatment promoted PGE2 and PGF2α secretion in a dose-dependent manner. In contrast, UCN2 dose-dependently inhibited PGE2 and PGF2α secretion. Their effects could be reversed by CRHR2 antagonist and CRHR2 siRNA. Mechanically, we showed that UCN and UCN3 suppressed cAMP production and led to Gi activation, while UCN2 promoted cAMP production and activated Gs signaling. Further, UCN and UCN3 could activate NF-κB and MAPK signaling pathways. These effects were dependent on Gi signaling. In contrast, UCN did not activate MAPK and NF-κB signaling. UCN and UCN3 stimulation of PG secretion was dependent on Gi/adenylyl cyclase (AC)/cAMP, NF-κB and MAPK signaling pathways, while UCN2 suppression of PG output was through Gs/AC/cAMP signaling pathways. Our data suggest that UCN, UCN2 and UCN3 can finely regulate the secretion of PGs via CRHR2, which facilities the functional status of uterus during pregnancy.

scholarly journals The Coumarin Derivative 5′-Hydroxy Auraptene Suppresses Osteoclast Differentiation via Inhibiting MAPK and c-Fos/NFATc1 Pathways

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Basem M. Abdallah ◽  
Enas M. Ali ◽  
Hany Elsawy ◽  
Gehan M. Badr ◽  
Ashraf M. Abdel-Moneim ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Gene Expression Regulation ◽  
Osteoclast Differentiation ◽  
Coumarin Derivative ◽  
Mapk Signaling ◽  
Tartrate Resistant Acid Phosphatase ◽  
Mouse Bone Marrow ◽  
Dependent Manner ◽  
Dose Dependent ◽  
Mapk Signaling Pathways

The phytochemical substances, coumarin derivatives, have demonstrated antiresorptive bone effects by suppressing osteoclast differentiation in vitro and in vivo. Recently, we have identified 5′-hydroxy auraptene (5′-HA), a coumarin derivative isolated from Lotus lalambensis Schweinf, as a novel stimulator for osteoblast differentiation. In this study, we investigated the effect of 5′-HA on osteoclast differentiation of mouse bone marrow (BM) cells. The effect of 5′-HA on BM cell proliferation and osteoclast differentiation was determined by measuring cell viability and tartrate-resistant acid phosphatase (TRAP) enzyme activity, quantification of TRAP+ multinucleated cells (TRAP+MNCs), and quantitative real-time PCR (qPCR) of osteoclastic gene expression. Regulation of NF-κB, c-Fos/NFATc1, and MAPK signaling pathways by 5′-HA during osteoclastogenesis was measured by the NF-κB reporter assay and Western blot analysis. 5′-HA significantly suppresses the receptor activator of NF-κB ligand (RANKL) induced osteoclast differentiation of BM cells in a dose-dependent manner. Consistently, treatment of BM cells with 5′-HA significantly inhibited RANKL-induced activation of NF-κB and c-Fos/NFATc1 pathways in a dose-dependent manner. Furthermore, RANKL-induced phosphorylation of ERK1/2, p-38, and JNK was significantly inhibited by 5′-HA in BM cells. In conclusion, we identified 5′-HA as a novel coumarin derivative that suppresses RANKL-induced osteoclastogenesis via inhibiting c-Fos/NFATc1 and MAPK signaling pathways.

Emodin induces hepatocellular carcinoma cell apoptosis through MAPK and PI3K/AKT signaling pathways in vitro and in vivo

2016 ◽  
Vol 36 (2) ◽  
pp. 961-967 ◽  
Author(s):  
Wanfu Lin ◽  
Maofeng Zhong ◽  
Huixia Yin ◽  
Yongan Chen ◽  
Qingxin Cao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathways ◽  
Cell Apoptosis ◽  
Carcinoma Cell ◽  
Akt Signaling ◽  
Hepatocellular Carcinoma Cell

scholarly journals Erianin suppresses hepatocellular carcinoma cells through down-regulation of PI3K/AKT, p38 and ERK MAPK signaling pathways

2020 ◽  
Vol 40 (7) ◽  
Author(s):  
Liang Yang ◽  
Yue Hu ◽  
Guanbao Zhou ◽  
Qi Chen ◽  
Zhenshun Song
Keyword(s):  
Hepatocellular Carcinoma ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Migration And Invasion ◽  
Tunel Staining ◽  
Dependent Manner ◽  
Erk Mapk ◽  
Mapk Signaling Pathways

Abstract Background: Hepatocellular carcinoma (HCC) is the dominant pathological type of primary liver cancer and no effective methods are available for its treatment. Erianin is a natural product extracted from Dendrobium, which possesses multiple pharmacological activities, including antioxidative and antitumor activity. Objective: To evaluate the anti-HCC activities of erianin and explore its underlying mechanism. Methods: MTT assay and Crystal Violet staining assay were used to select the non-toxic concentrations for the subsequent experiments. The colony formation assay and PCNA fluorescent staining were used to investigate the antiproliferative effects of erianin on human SMMC-7721 and HepG2 cells. Wound healing and transwell test were used to analyze cell migration and invasion. Caspase3 and Tunel staining were used to detect apoptosis. Western blot was used to examine the expression levels of proteins associated with invasion and key proteins in the phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), p38 and ERK mitogen-activated protein kinase (MAPK) signaling pathways. Results: Erianin inhibited HCC cell proliferation in a dose-dependent manner. Decreased migration rate and invaded cells were observed with erianin supplement. The expression of invasion-associated proteins in the erianin group was also down-regulated. Besides, more apoptotic cells were observed after erianin treatment. For the molecular mechanism, erianin inhibited the phosphorylation of Akt, ERK and P38 in the PI3K/Akt and ERK/P38 pathway. Conclusion: We demonstrated, for the first time, that erianin inhibited the proliferation, migration, invasion and induced the apoptosis of HCC through PI3K/Akt, p38 and ERK MAPK signaling pathway, indicating that erianin is a promising agent for the HCC treatment.

scholarly journals Emodin promotes apoptosis of human endometrial cancer through regulating the MAPK and PI3K/ AKT pathways

2019 ◽  
Vol 13 (1) ◽  
pp. 489-496 ◽  
Author(s):  
Jun Jiang ◽  
Nanyang Zhou ◽  
Pian Ying ◽  
Ting Zhang ◽  
Ruojia Liang ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Signaling Pathways ◽  
Tumor Development ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Western Blot Assay ◽  
Anti Oxidant ◽  
Underlying Mechanisms ◽  
Induced Apoptosis ◽  
Dose Dependent

AbstractEmodin, a major component of rhubarb, has anti-tumor effects in a variety of cancers, influencing multiple steps of tumor development through modulating several signaling pathways. The aim of this study is to examine the effect of emodin on cell apoptosis and explore the underlying mechanisms in human endometrial cancer cells. Here we report that emodin can inhibit KLE cell proliferation and induce apoptosis in a time- and dose-dependent manner. Western blot assay found that emodin was involved in MAPK and PI3K/Akt signaling pathways. Specifically, emodin significantly suppressed the phosphorylation of AKT, and enhanced the phosphorylation of MAPK pathways. Furthermore, the generation of reactive oxygen species (ROS) was up-regulated in KLE cells upon treatment with emodin, while the anti-oxidant agent N-acetyl cysteine (NAC) can inhibit emodin-induced apoptosis and promote the activation of AKT and Bcl-2. Taken together, we revealed that emodin may induce apoptosis in KLE cells through regulating the PI3K/AKT and MAPK signaling pathways, indicating the importance of emodin as an anti-tumor agent.

scholarly journals Dihydroartemisinin Inhibits Proliferation and Induces Apoptosis of Human Hepatocellular Carcinoma Cell by Upregulating Tumor Necrosis Factor via JNK/NF-κB Pathways

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Long Wu ◽  
Yanlei Cheng ◽  
Junjian Deng ◽  
Weiping Tao ◽  
Junjie Ye
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Differentially Expressed Genes ◽  
Carcinoma Cell ◽  
Expression Profiles ◽  
Human Hepatocellular Carcinoma ◽  
Differentially Expressed ◽  
Venn Diagram ◽  
Dependent Manner ◽  
Hepatocellular Carcinoma Cell

Background. Dihydroartemisinin (DHA) is a predominant compound in Artemisia annua L., and it has been shown to inhibit tumorigenesis. Methods. In this study, the antitumor potential of DHA was investigated in the MHCC97-L hepatocellular carcinoma cell line. Cells were treated at various concentrations of DHA, and then the cell cycle, viability, and DNA synthesis were measured to evaluate cell proliferation. Furthermore, the expression of genes and proteins related to proliferation and apoptosis was measured to determine the effects of DHA. Finally, the mechanism was investigated using RNA-sequencing to identify differentially expressed genes and signaling pathways, and JNK/NF-κB pathways were evaluated with Western blotting. Results. Cells were treated with a concentration range of DHA from 1 to 100 μM, and cell proliferation was suppressed in a dose-dependent manner. In addition, the genes and proteins involved in typical cellular functions of MHCC97-L cells were significantly inhibited. DHA treatment downregulated the angiogenic gene ANGPTL2 and the cell proliferation genes CCND1, E2F1, PCNA, and BCL2. DHA treatment significantly upregulated the apoptotic genes CASP3, CASP8, CASP9, and TNF. Global gene expression profiles identified 2064 differentially expressed genes (DEGs). Among them, 744 were upregulated and 1320 were downregulated. Furthermore, MAPK, NF-kappa B, and TNF pathways were enriched based on the DEGs, and the consensus DEG was identified as TNF using a Venn diagram of those pathways. DHA promoted phosphorylation of JNK, inhibited nuclear p65, and then significantly induced TNF-α synthesis. Conclusion. DHA inhibited cell proliferation and induced apoptosis in human hepatocellular carcinoma cells by upregulating TNF expression via JNK/NF-κB pathways.

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.

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