Browse
Submit Data
Databases
API
Help

Dataset Information

20 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TR35 Exerts Anti-tumor Effects by Modulating Mitogen-Activated Protein Kinase and STAT3 Signaling in Lung Cancer Cells

ABSTRACT: Cancer is a complex disease extremely dependent on its microenvironment and is highly regulated by a variety of stimuli inside and outside the cell. Evidence suggests that active camel whey fraction (TR35) confer anti-tumor effects in non-small cell lung cancer (NSCLC). However, its exact mechanisms remain elusive. Here, we investigated the mechanisms underlying suppression of NSCLC cell growth and proliferation by TR35. Treatment of A549 and H1299 cells with TR35 suppressed their growth and enhanced apoptosis, as revealed by CCK-8, colony formation and flow cytometric analyses. We find that TR35 suppresses tumor growth in a xenograft nude mouse model without losses in body weight. RNA-seq and KEGG pathway analyses showed that the DEGs were enriched in mitogen-activated protein kinase (MAPK) and Jak-STAT signaling pathways. After test the key factors’ activity associated with these pathways by Immunohistochemical (IHC) staining and western blotting, the activation of JNK phosphorylation and inhibition of p38 and STAT3 phosphorylation was observed both in TR35 treated lung cancer cell and tumor tissue. Taken together, these results showed that TR35 play a significant role in the NSCLC progression in the tumor microenvironment via MAPK and Jak-STAT signaling, highlighting TR35 as a potential therapeutic agent against lung cancer.

SUBMITTER: Shi Z

PROVIDER: S-EPMC8573214 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Leonurine Exerts Anti-Catabolic and Anti-Apoptotic Effects via Nuclear Factor kappa B (NF-?B) and Mitogen-Activated Protein Kinase (MAPK) Signaling Pathways in Chondrocytes.

Project description:BACKGROUND Leonurine confers neuroprotection, inhibits myocardial apoptosis, ameliorates endothelial dysfunction, and shows anti-inflammatory effects, and may be beneficial for clinical applications. However, the effects of leonurine on chondrocytes remain unknown. Here, we investigated the protective role of leonurine in rat chondrocytes. MATERIAL AND METHODS To explore the potential therapeutic effect of leonurine against osteoarthritis (OA), rat chondrocytes were treated with IL-1ß along with different concentrations of leonurine in vitro. The levels of matrix metalloproteinases (MMPs), ADAMTS, Bax, and Bcl-2 were measured by PCR, ELISA, and Western blotting. Caspase-3 activity in chondrocytes was determined using a caspase-3 activity assay. Western blotting was also performed to examine activation of the NF-kappaB and mitogen-activated protein kinase (MAPK) pathways to elucidate the likely regulatory mechanisms. RESULTS Leonurine counteracted IL-1ß-induced production of MMP-1, MMP-13, ADAMTS-4, and ADAMTS-5. Leonurine treatment reduced both the mRNA and protein levels of Bax and increased the level of Bcl-2. Leonurine also inhibited the activity of caspase-3 in IL-1ß-induced chondrocytes. Furthermore, the activation of MAPK and phosphorylation of p65 were suppressed by leonurine. CONCLUSIONS The results of this study indicate that leonurine exerts anti-catabolic and anti-apoptotic effects in chondrocytes in vitro via suppression of the NF-kappaB and MAPK signaling pathways.

| S-EPMC6714594 | biostudies-literature

Physalin A exerts anti-tumor activity in non-small cell lung cancer cell lines by suppressing JAK/STAT3 signaling.

Project description:The signal transducers and activators of transcription 3 (STAT3) signaling pathway plays critical roles in the pathogenesis and progression of various human cancers, including non-small cell lung cancer (NSCLC). In this study, we aimed to evaluate the therapeutic potential of physalin A, a bioactive withanolide derived from Physalis alkekengi var. francheti used in traditional Chinese medicine, was evaluated in human NSCLC cells. Its and determined whether it effect oninhibited both constitutive and induced STAT3 activity, through repressing the phosphorylation levels of JAK2 and JAK3, resulting in anti-proliferation and pro-apoptotic effects on NSCLC cells was also determined, and. theThe antitumor effects of physalin A were also validated usingin an in vivo mouse xenograft models of NSCLC cells. Physalin A had anti-proliferative and pro-apoptotic effects in NSCLC cells with constitutively activated STAT3; it also suppressed both constitutive and induced STAT3 activity by modulating the phosphorylation of JAK2 and JAK3. Furthermore, physalin A abrogated the nuclear translocation and transcriptional activity of STAT3, thereby decreasing the expression levels of STAT3, its target genes, such as Bcl-2 and XIAP. Knockdown of STAT3 expression by small interfering RNA (siRNA) significantly enhanced the pro-apoptotic effects of physalin A in NSCLC cells. Moreover, physalin A significantly suppressed tumor xenograft growth. Thus, as an inhibitor of JAK2/3-STAT3 signaling, physalin A, has potent anti-tumor activities, which may facilitate the development of a therapeutic strategy for treating NSCLC.

| S-EPMC4891052 | biostudies-literature

PLOD3 suppression exerts an anti-tumor effect on human lung cancer cells by modulating the PKC-delta signaling pathway.

Project description:Current lung cancer treatments are far from satisfactory; thus, finding novel treatment targets is crucial. We recently identified procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3), which is involved in fibrosis and tissue remodeling as a radioresistance-related protein in lung cancer cells; however, its mechanism is unclear. In this study, we designed human PLOD3-specific short interfering (si)RNAs and tested their effects on tumor growth inhibition in vitro and in vivo. PLOD3 knockdown overcame chemoresistance and decreased radioresistance by inducing caspase-3-dependent apoptosis in lung cancer cells. Furthermore, PLOD3 interacted with PKCδ to activate caspase-2,4-dependent apoptosis through ER-stress-induced IRE1α activation and the downstream unfolded-protein response pathway. In a mouse xenograft model, PLOD3 knockdown promoted radiation-induced tumor growth inhibition, without side effects. Moreover, lung cancer patients with high PLOD3 expression showed poorer prognosis than those with low PLOD3 expression upon radiotherapy, suggesting that PLOD3 promotes tumor growth. Therefore, PLOD3 siRNA suppresses radioresistance and chemoresistance by inducing apoptosis and renders PLOD3 as a candidate lung cancer biomarker. PLOD3 gene therapy might enhance the efficacy of radiotherapy or chemotherapy in lung cancer patients.

| S-EPMC6377650 | biostudies-literature

Mitogen-Activated Protein Kinase Cascades in Plant Hormone Signaling.

Project description:Mitogen-activated protein kinase (MAPK) modules play key roles in the transduction of environmental and developmental signals through phosphorylation of downstream signaling targets, including other kinases, enzymes, cytoskeletal proteins or transcription factors, in all eukaryotic cells. A typical MAPK cascade consists of at least three sequentially acting serine/threonine kinases, a MAP kinase kinase kinase (MAPKKK), a MAP kinase kinase (MAPKK) and finally, the MAP kinase (MAPK) itself, with each phosphorylating, and hence activating, the next kinase in the cascade. Recent advances in our understanding of hormone signaling pathways have led to the discovery of new regulatory systems. In particular, this research has revealed the emerging role of crosstalk between the protein components of various signaling pathways and the involvement of this crosstalk in multiple cellular processes. Here we provide an overview of current models and mechanisms of hormone signaling with a special emphasis on the role of MAPKs in cell signaling networks. One-sentence summary: In this review we highlight the mechanisms of crosstalk between MAPK cascades and plant hormone signaling pathways and summarize recent findings on MAPK regulation and function in various cellular processes.

| S-EPMC6187979 | biostudies-literature

Pharmacology and anti-tumor activity of RWJ67657, a novel inhibitor of p38 mitogen activated protein kinase.

Project description:Endocrine therapy resistance is a primary cause of clinical breast cancer treatment failure. The p38 mitogen activated protein kinase (MAPK) signaling pathway is known to promote ligand independent tumor growth and resistance to endocrine therapy. In this study, we investigated the therapeutic potential of the p38 inhibitor RWJ67657 in the treatment of tamoxifen resistant MDA-MB-361 cells. RWJ67657 dose-dependently decreased both basal and stimulated activation of p38 MAPK signaling in this drug resistant cell system. Decreased activation of p38 by RWJ67657 resulted in inhibition of the downstream p38 targets hsp27 and MAPKAPK. Diminished p38 signaling resulted in inhibition of p38-medated gene transcription. Furthermore, pharmacological inhibition of p38 by RWJ67657 decreased biological effects of p38, including ER-mediated gene expression and clonogenic survival in a dose-dependent manner. Animal studies revealed significantly decreased p38 signaling in vivo following exposure to RWJ67657. Treatment with the inhibitor markedly decreased phosphorylation of p38 in MDA-MB-361 tumors, leading to decreased transcription of both Fra-1 and progesterone receptor. Utilizing well-established xenograft tumor models, we demonstrated that RWJ67657 exhibits potent anti-tumor properties. Treatment with RWJ67657 markedly decreased tamoxifen resistant tumor growth, both in the presence and absence of estrogen. Taken together, our findings demonstrate the therapeutic potential of targeting the p38-MAPK signaling cascade in the treatment of endocrine resistant breast cancer.

| S-EPMC3410584 | biostudies-literature

Remodeling tumor-associated macrophage for anti-cancer effects by rational design of irreversible inhibition of mitogen-activated protein kinase-activated protein kinase 2.

Project description:Mitogen-activated protein kinase-activated protein kinase 2 (MK2) emerges as a pivotal target in developing anti-cancer therapies. The limitations of ATP-competitive inhibitors, due to insufficient potency and selectivity, underscore the urgent need for a covalent irreversible MK2 inhibitor. Our initial analyses of The Cancer Genome Atlas database revealed MK2's overexpression across various cancer types, especially those characterized by inflammation, linking it to poor prognosis and highlighting its significance. Investigating MK2's kinase domain led to the identification of a unique cysteine residue, enabling the creation of targeted covalent inhibitors. Compound 11 was developed, demonstrating robust MK2 inhibition (IC50 = 2.3 nM) and high selectivity. It binds irreversibly to MK2, achieving prolonged signal suppression and reducing pathological inflammatory cytokines in macrophages. Furthermore, compound 11 or MK2 knockdown can inhibit the tumor-promoting macrophage M2 phenotype in vitro and in vivo. In macrophage-rich tumor model, compound 11 notably slowed growth in a dose-dependent manner. These findings support MK2 as a promising anticancer target, especially relevant in cancers fueled by inflammation or dominated by macrophages, and provide compound 11 serving as an invaluable chemical tool for exploring MK2's functions.

| S-EPMC11233931 | biostudies-literature

Trilobolide-6-O-isobutyrate exerts anti-tumor effects on cholangiocarcinoma cells through inhibiting JAK/STAT3 signaling pathway

Project description: Not available

| S-EPMC10915568 | biostudies-literature

Noise exposure immediately activates cochlear mitogen-activated protein kinase signaling.

Project description:Noise-induced hearing loss (NIHL) is a major public health issue worldwide. Uncovering the early molecular events associated with NIHL would reveal mechanisms leading to the hearing loss. Our aim is to investigate the immediate molecular responses after different levels of noise exposure and identify the common and distinct pathways that mediate NIHL. Previous work showed mice exposed to 116 decibels sound pressure level (dB SPL) broadband noise for 1 h had greater threshold shifts than the mice exposed to 110 dB SPL broadband noise, hence we used these two noise levels in this study. Groups of 4-8-week-old CBA/CaJ mice were exposed to no noise (control) or to broadband noise for 1 h, followed by transcriptome analysis of total cochlear RNA isolated immediately after noise exposure. Previously identified and novel genes were found in all data sets. Following exposure to noise at 116 dB SPL, the earliest responses included up-regulation of 243 genes and down-regulation of 61 genes, while a similar exposure at 110 dB SPL up-regulated 155 genes and down-regulated 221 genes. Bioinformatics analysis indicated that mitogen-activated protein kinase (MAPK) signaling was the major pathway in both levels of noise exposure. Nevertheless, both qualitative and quantitative differences were noticed in some MAPK signaling genes, after exposure to different noise levels. Cacna1b , Cacna1g , and Pla2g6 , related to calcium signaling were down-regulated after 110 dB SPL exposure, while the fold increase in the expression of Fos was relatively lower than what was observed after 116 dB SPL exposure. These subtle variations provide insight on the factors that may contribute to the differences in NIHL despite the activation of a common pathway.

| S-EPMC4591925 | biostudies-literature

Oocyte aging is controlled by mitogen-activated protein kinase signaling.

Project description:Oogenesis is one of the first processes to fail during aging. In women, most oocytes cannot successfully complete meiotic divisions already during the fourth decade of life. Studies of the nematode Caenorhabditis elegans have uncovered conserved genetic pathways that control lifespan, but our knowledge regarding reproductive aging in worms and humans is limited. Specifically, little is known about germline internal signals that dictate the oogonial biological clock. Here, we report a thorough characterization of the changes in the worm germline during aging. We found that shortly after ovulation halts, germline proliferation declines, while apoptosis continues, leading to a gradual reduction in germ cell numbers. In late aging stages, we observed that meiotic progression is disturbed and crossover designation and DNA double-strand break repair decrease. In addition, we detected a decline in the quality of mature oocytes during aging, as reflected by decreasing size and elongation of interhomolog distance, a phenotype also observed in human oocytes. Many of these altered processes were previously attributed to MAPK signaling variations in young worms. In support of this, we observed changes in activation dynamics of MPK-1 during aging. We therefore tested the hypothesis that MAPK controls oocyte quality in aged worms using both genetic and pharmacological tools. We found that in mutants with high levels of activated MPK-1, oocyte quality deteriorates more rapidly than in wild-type worms, whereas reduction of MPK-1 levels enhances quality. Thus, our data suggest that MAPK signaling controls germline aging and could be used to attenuate the rate of oogenesis quality decline.

| S-EPMC8208789 | biostudies-literature

Scaffolding of Mitogen-Activated Protein Kinase Signaling by β-Arrestins.

Project description:β-arrestins were initially identified to desensitize and internalize G-protein-coupled receptors (GPCRs). Receptor-bound β-arrestins also initiate a second wave of signaling by scaffolding mitogen-activated protein kinase (MAPK) signaling components, MAPK kinase kinase, MAPK kinase, and MAPK. In particular, β-arrestins facilitate ERK1/2 or JNK3 activation by scaffolding signal cascade components such as ERK1/2-MEK1-cRaf or JNK3-MKK4/7-ASK1. Understanding the precise molecular and structural mechanisms of β-arrestin-mediated MAPK scaffolding assembly would deepen our understanding of GPCR-mediated MAPK activation and provide clues for the selective regulation of the MAPK signaling cascade for therapeutic purposes. Over the last decade, numerous research groups have attempted to understand the molecular and structural mechanisms of β-arrestin-mediated MAPK scaffolding assembly. Although not providing the complete mechanism, these efforts suggest potential binding interfaces between β-arrestins and MAPK signaling components and the mechanism for MAPK signal amplification by β-arrestin-mediated scaffolding. This review summarizes recent developments of cellular and molecular works on the scaffolding mechanism of β-arrestin for MAPK signaling cascade.

| S-EPMC8778048 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data