Signaling pathways via NK1 receptors and their desensitization in an AR42J cell line

Background: Melanin plays a crucial role in camouflage, social communication and protection against harmful ultraviolet radiations. Melanin is synthesized by melanocytes through melanogenesis and several intrinsic and extrinsic factors are involved during the process. Any change occuring in the normal melanogenesis process can cause severe pigmentation problems of hypopigmentation or hyperpigmentation. Objective: The present study is based on the evaluation of the effect of thymoquinone on melanogenesis and their possible mechanism of action using the B16F10 melanoma cell line for the production via blocking signaling pathways. Methods: Phase contrast microscopy, cell viability, tyrosinase activity, melanin content and western blot analysis were used in the present study. Results: In the present investigation, cultured melanocytes exhibit that the stimulation of melanin synthesis when treated with thymoquinone. Tyrosinase activity and melanin production in B16F10 melanoma cell line was increased in doze-dependent manner. In western blot, we investigated the involvement of the cAMP/PKA pathway in thymoquinone induced melanogenesis. It was observed protein kinase inhibitors PKA, PKC, PKB and MEK1 decreased the stimulatory effects of thymoquinone from 11.45- fold value to 8.312, 6.631, 4.51, and 7.211-fold value, respectively. However, the results also prove that thymoquinone may partially induce tyrosinase expression via PKA, PKB, PKC and MEK1 signaling pathways. Conclusion: The present finding proposed that thymoquinone is a protective challenger for melanogenesis and it might be useful for the treatment of hypopigmentary disorders.

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Trifolium Flavonoids Overcome Gefitinib Resistance of Non-Small-Cell Lung Cancer Cell by Suppressing ERK and STAT3 Signaling Pathways

BioMed Research International ◽

10.1155/2020/2491304 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Zhiqiang Wu ◽

Bin Xu ◽

Zhiyi Yu ◽

Qin He ◽

Zhuyuan Hu ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Signaling Pathways ◽

Cell Line ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

Stat3 Signaling ◽

Induced Apoptosis ◽

Gefitinib Resistance

Gefitinib is a tyrosine kinase inhibitor of EGFR (epidermal growth factor receptor) and represents the first-line treatment for EGFR mutation patients with NSCLC (non-small-cell lung cancer) therapeutics. However, NSCLC patients are inclined to develop acquired gefitinib drug resistance through nowadays, unarticulated mechanisms of chemoresistance. Here, we investigated the role of TF (Trifolium flavonoids) on sensitizing gefitinib resistance in NSCLC cells and revealed its potential mechanism of action. We demonstrated that TF exerted significantly potential chemosensitivity in gefitinib resistant NSCLC cells. MTT assay and cytological methods were used to analyze cell viability and apoptosis in NSCLC cell line PC-9R. Both TF and gefitinib suppressed PC-9R cell growth in a dose-dependent manner. Subtoxic concentrations of TF did significantly augment gefitinib-induced apoptosis in PC-9R cell line. The TF promoted chemosensitivity was major mediated by the PARP and caspases activation. Meanwhile, the TF promoted chemosensitivity also decreased the expression of Bcl-2 and Mcl-1. Finally, TF significantly reduced the phosphorylation levels of STAT3 and ERK. Altogether, the results of the present study indicated the potential mechanisms of chemosensitivity of TF in gefitinib-induced apoptosis of NSCLC by downregulating ERK and STAT3 signaling pathways and Bcl2 and Mcl-1 expression and a promising application of TF in therapy of NSCLC with gefitinib resistant.

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COL2A1 Is a Novel Biomarker of Melanoma Tumor Repopulating Cells

Biomedicines ◽

10.3390/biomedicines8090360 ◽

2020 ◽

Vol 8 (9) ◽

pp. 360

Author(s):

Bhavana Talluri ◽

Kshitij Amar ◽

Michael Saul ◽

Tasnim Shireen ◽

Vjollca Konjufca ◽

...

Keyword(s):

Signaling Pathways ◽

Cell Line ◽

Aerobic Glycolysis ◽

Parental Control ◽

Control Cell ◽

Differentially Expressed Gene ◽

Gene Clusters ◽

Rna Seq ◽

Novel Biomarkers ◽

Gene Regulatory

Soft 3D-fibrin-gel selected tumor repopulating cells (TRCs) from the B16F1 melanoma cell line exhibit extraordinary self-renewal and tumor-regeneration capabilities. However, their biomarkers and gene regulatory features remain largely unknown. Here, we utilized the next-generation sequencing-based RNA sequencing (RNA-seq) technique to discover novel biomarkers and active gene regulatory features of TRCs. Systems biology analysis of RNA-seq data identified differentially expressed gene clusters, including the cell adhesion cluster, which subsequently identified highly specific and novel biomarkers, such as Col2a1, Ncam1, F11r, and Negr1. We validated the expression of these genes by real-time qPCR. The expression level of Col2a1 was found to be relatively low in TRCs but twenty-fold higher compared to the parental control cell line, thus making the biomarker very specific for TRCs. We validated the COL2A1 protein by immunofluorescence microscopy, showing a higher expression of COL2A1 in TRCs compared to parental control cells. KEGG pathway analysis showed the JAK/STAT, hypoxia, and Akt signaling pathways to be active in TRCs. Besides, the aerobic glycolysis pathway was found to be very active, indicating a typical Warburg Effect on highly tumorigenic cells. Together, our study revealed highly specific biomarkers and active cell signaling pathways of melanoma TRCs that can potentially target and neutralize TRCs.

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Outside-In Signaling of Soluble and Solid-Phase Fibrinogen Through Integrin ΙΙbβ3 Is Different and Cooperative With Each Other in a Megakaryoblastic Leukemia Cell Line, CMK

Blood ◽

10.1182/blood.v92.4.1277 ◽

1998 ◽

Vol 92 (4) ◽

pp. 1277-1286 ◽

Cited By ~ 19

Author(s):

Yumi Tohyama ◽

Kaoru Tohyama ◽

Misao Tsubokawa ◽

Momoyo Asahi ◽

Yataro Yoshida ◽

...

Keyword(s):

Cell Adhesion ◽

Signaling Pathways ◽

Cell Line ◽

Tyrosine Phosphorylation ◽

Solid Phase ◽

Leukemia Cell ◽

Leukemia Cell Line ◽

Megakaryoblastic Leukemia ◽

Integrin Β3 ◽

Coated Plate

Abstract The function and the outside-in signaling pathways of IIbβ3 were examined in relation to cell adhesion using a megakaryoblastic leukemia cell line, CMK. After 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment, the cells adhered to the culture plate and underwent megakaryocytic differentiation with expression of IIbβ3. Binding of soluble fibrinogen to the cells via IIbβ3 was dependent on cell adhesion. Cell detaching reduced the affinity of this integrin for soluble fibrinogen, although its surface expression was almost unchanged. In contrast, detached cells became tightly adherent to the fibrinogen-coated plate (solid-phase fibrinogen). The same ligand, fibrinogen, present either in soluble or solid-phase form, triggered differential signaling pathways mediated by IIbβ3. By the stimulation with soluble fibrinogen, Syk was tyrosine-phosphorylated but FAK was dephosphorylated, whereas solid-phase fibrinogen promptly caused tyrosine phosphorylation of FAK followed by delayed phosphorylation of Syk. In addition, the binding of soluble fibrinogen to the cells adherent to fibrinogen-coated plate resulted in tyrosine phosphorylation of integrin β3 and a complex formation of integrin β3 with Syk. This implies the cooperation of both soluble and solid-phase fibrinogen-mediated signaling pathways. © 1998 by The American Society of Hematology.

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Buthionine sulfoximine, an inhibitor of glutathione biosynthesis, induces expression of soluble epoxide hydrolase and markers of cellular hypertrophy in a rat cardiomyoblast cell line: Roles of the NF-κB and MAPK signaling pathways

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2015.01.005 ◽

2015 ◽

Vol 82 ◽

pp. 1-12 ◽

Cited By ~ 23

Author(s):

Ghada Abdelhamid ◽

Ayman O.S. El-Kadi

Keyword(s):

Signaling Pathways ◽

Cell Line ◽

Epoxide Hydrolase ◽

Buthionine Sulfoximine ◽

Soluble Epoxide Hydrolase ◽

Mapk Signaling ◽

Glutathione Biosynthesis ◽

Cellular Hypertrophy ◽

Mapk Signaling Pathways

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pp60c-src is a positive regulator of growth factor-induced cell scattering in a rat bladder carcinoma cell line.

The Journal of Cell Biology ◽

10.1083/jcb.131.3.761 ◽

1995 ◽

Vol 131 (3) ◽

pp. 761-773 ◽

Cited By ~ 56

Author(s):

J M Rodier ◽

A M Vallés ◽

M Denoyelle ◽

J P Thiery ◽

B Boyer

Keyword(s):

Growth Factor ◽

Signaling Pathways ◽

Cell Line ◽

Intracellular Signaling ◽

Carcinoma Cell ◽

Biological Activities ◽

Dominant Negative ◽

Carcinoma Cell Line ◽

Dominant Negative Mutant ◽

Cell Scattering

The NBT-II rat carcinoma cell line exhibits two mutually exclusive responses to FGF-1 and EGF, entering mitosis at cell confluency while undergoing an epithelium-to-mesenchyme transition (EMT) when cultured at subconfluency. EMT is characterized by acquisition of cell motility, modifications of cell morphology, and cell dissociation correlating with the loss of desmosomes from cellular cortex. The pleiotropic effects of EGF and FGF-1 on NBT-II cells suggest that multiple signaling pathways may be activated. We demonstrate here that growth factor activation is linked to at least two intracellular signaling pathways. One pathway leading to EMT involves an early and sustained stimulation of pp60c-src kinase activity, which is not observed during the growth factor-induced entry into the cell cycle. Overexpression of normal c-src causes a subpopulation of cells to undergo spontaneous EMT and sensitizes the rest of the population to the scattering activity of EGF and FGF-1 without affecting their mitogenic responsiveness. Addition of cholera toxin, a cAMP-elevating agent, severely perturbs growth factor induction of EMT without altering pp60c-src activation, therefore demonstrating that cAMP blockade takes place downstream or independently of pp60c-src. On the other hand, overexpression of a mutated, constitutively activated form of pp60c-src does not block cell dispersion while strongly inhibiting growth factor-induced entry into cell division. Moreover, stable transfection of a dominant negative mutant of c-src inhibits the scattering response without affecting mitogenesis induced by the growth factors. Altogether, these results suggest a role for pp60c-src in epithelial cell scattering and indicate that pp60c-src might contribute unequally to the two separate biological activities engendered by a single signal.

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Abstract A10: Simultaneous block of angiogenesis through PI3K-AMPK/AKT/mTOR signaling pathways after treatment with metformin and LY294002 in canine mammary tumor cell line

10.1158/1538-8514.tumang15-a10 ◽

2015 ◽

Author(s):

Marina Gobbe Moschetta ◽

Larissa Bazela Maschio ◽

Bruna Victorasso Jardim-Perassi ◽

Gabriela Bottaro Gelaleti ◽

Camila Leonel ◽

...

Keyword(s):

Tumor Cell ◽

Signaling Pathways ◽

Cell Line ◽

Mammary Tumor ◽

Tumor Cell Line ◽

Mtor Signaling ◽

Canine Mammary Tumor ◽

Mammary Tumor Cell ◽

Mammary Tumor Cell Line

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7-Ketocholesterol and cholestane-triol increase expression of SMO and LXRα signaling pathways in a human breast cancer cell line

Biochemistry and Biophysics Reports ◽

10.1016/j.bbrep.2018.12.008 ◽

2019 ◽

Vol 19 ◽

pp. 100604 ◽

Cited By ~ 3

Author(s):

Debora Levy ◽

Thatiana Correa de Melo ◽

Beatriz A. Oliveira ◽

Jessica L. Paz ◽

Fabio A. de Freitas ◽

...

Keyword(s):

Breast Cancer ◽

Signaling Pathways ◽

Cell Line ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Breast Cancer Cell Line ◽

Human Breast Cancer ◽

Cancer Cell Line ◽

Human Breast Cancer Cell ◽

Human Breast

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Amiloride and analogues inhibit Na(+)-H+ exchange and cell proliferation in AR42J pancreatic cell line

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1990.259.5.g842 ◽

1990 ◽

Vol 259 (5) ◽

pp. G842-G849 ◽

Cited By ~ 5

Author(s):

M. Delvaux ◽

M. J. Bastie ◽

J. Chentoufi ◽

E. J. Cragoe ◽

N. Vaysse ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Line ◽

Calf Serum ◽

Dependent Manner ◽

Pancreatic Cell ◽

Blocking Agents ◽

Ar42j Cells ◽

Ic50 Values ◽

Ar42j Cell ◽

Na Uptake

To study the relation between activation of the Na(+)-H+ antiporter and gastrointestinal cell proliferation, we characterized this antiporter in a pancreatic cell line (AR42J) and studied the effects of mitogenic and nonmitogenic agents as well as those of Na(+)-H+ exchange blocking agents on DNA synthesis. Characteristics of amiloride-sensitive Na+ uptake were those of the Na(+)-H+ exchanger: 1) Na+ uptake was increased by intracellular acidification and depended on external [Na+] and pH; 2) concentrations for half-maximal inhibition (IC50) of Na+ uptake (3 mM [Na+] in medium) were 40 nM 5-(N,N-hexamethylene)amiloride (HA) less than 0.1 microM 5-(N-ethyl-N-isopropyl)amiloride (EIPA) less than 1 microM 5-(N,N-dimethyl)-amiloride (DMA) less than 40 microM amiloride; 3) IC50 for amiloride and analogues to inhibit Na+ uptake depended on [Na+] in medium (in 25 mM Na+ medium, the IC50 values were higher than in 3 mM and were 1 microM EIPA less than 10 microM DMA less than 0.3 mM amiloride). Growth factors for AR42J cells (dialyzed fetal calf serum and epidermal growth factor) activated Na+ uptake in a dose-dependent manner. Bombesin, which is nonmitogenic for AR42J cells, also increased Na+ uptake, indicating that activation of the antiporter is not sufficient to initiate cell proliferation in the AR42J cell line. The effects of Na(+)-H+ exchange blocking agents were tested on serum-stimulated cell proliferation. Decreasing external Na+ dramatically decreased AR42J cell proliferation. Amiloride and analogues inhibited [3H]thymidine incorporation in the same range of concentrations as that with which they inhibited Na(+)-H+ exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

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