c-FLIPp43 induces activation of the nuclear factor-κB signaling pathway in a dose-dependent manner in the A375 melanoma cell line

Imiqualines (imidazoquinoxaline derivatives) are anticancer compounds with high cytotoxic activities on melanoma cell lines. The first generation of imiqualines, with two lead compounds (EAPB0203 and EAPB0503), shows remarkable in vitro (IC50 = 1 570 nM and IC50 = 200 nM, respectively, on the A375 melanoma cell line) and in vivo activity on melanoma xenografts. The second generation derivatives, EAPB02302 and EAPB02303, are more active, with IC50 = 60 nM and IC50 = 10 nM, respectively, on A375 melanoma cell line. The aim of this study was to optimize the bioavailability of imiqualine derivatives, without losing their intrinsic activity. For that, we achieved chemical modulation on the second generation of imiqualines by conjugating amino acids on position 4. A new series of twenty-five compounds was efficiently synthesized by using microwave assistance and tested for its activity on the A375 cell line. In the new series, compounds 11a, 9d and 11b show cytotoxic activities less than second generation compounds, but similar to that of the first generation ones (IC50 = 403 nM, IC50 = 128 nM and IC50 = 584 nM, respectively). The presence of an amino acid leads to significant enhancement of the water solubility for improved drugability.

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Antitumor potential of novel betulin derivative on human A375 melanoma cell line

Frontiers in Immunology ◽

10.3389/conf.fimmu.2013.02.00715 ◽

2013 ◽

Vol 4 ◽

Author(s):

Bulatovic Mirna ◽

Mojic Marija ◽

Kaludjerovic Goran ◽

Miljkovic Djordje ◽

Stosic-Grujicic Stanislava ◽

...

Keyword(s):

Cell Line ◽

Melanoma Cell ◽

Melanoma Cell Line ◽

Antitumor Potential ◽

A375 Melanoma Cell Line ◽

A375 Melanoma

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Platelet-Activating Factor Induces Up-regulation of Antiapoptotic Factors in a Melanoma Cell Line through Nuclear Factor-κB Activation

Cancer Research ◽

10.1158/0008-5472.can-05-3186 ◽

2006 ◽

Vol 66 (9) ◽

pp. 4681-4686 ◽

Cited By ~ 29

Author(s):

Kook Heon Seo ◽

Hyun-Mi Ko ◽

Han-A Kim ◽

Jung-Hwa Choi ◽

Sung Jun Park ◽

...

Keyword(s):

Cell Line ◽

Melanoma Cell ◽

Melanoma Cell Line ◽

Platelet Activating Factor ◽

Nuclear Factor Κb ◽

Nuclear Factor

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A Combination Therapy of Cisplatin and Lovastatin Reduces Ras Activation in an A375 Melanoma Cell Line

The FASEB Journal ◽

10.1096/fasebj.2020.34.s1.04914 ◽

2020 ◽

Vol 34 (S1) ◽

pp. 1-1

Author(s):

Nicole Kuss Shock ◽

Shere K. Byrd

Keyword(s):

Combination Therapy ◽

Cell Line ◽

Melanoma Cell ◽

Melanoma Cell Line ◽

Ras Activation ◽

A375 Melanoma Cell Line ◽

A375 Melanoma

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Insight into Mechanistic Action of Thymoquinone Induced Melanogenesis in Cultured Melanocytes

Protein and Peptide Letters ◽

10.2174/0929866526666190506114604 ◽

2019 ◽

Vol 26 (12) ◽

pp. 910-918

Author(s):

Kamal U. Zaidi ◽

Firoz N. Khan ◽

Sharique A. Ali ◽

Kausar P. Khan

Keyword(s):

Western Blot ◽

Signaling Pathways ◽

Cell Line ◽

Melanoma Cell ◽

Melanoma Cell Line ◽

Protein Kinase Inhibitors ◽

Tyrosinase Activity ◽

Dependent Manner ◽

B16f10 Melanoma ◽

B16f10 Melanoma Cell

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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α-Lipoic acid suppresses osteoclastogenesis despite increasing the receptor activator of nuclear factor κB ligand/osteoprotegerin ratio in human bone marrow stromal cells

Journal of Endocrinology ◽

10.1677/joe.1.05995 ◽

2005 ◽

Vol 185 (3) ◽

pp. 401-413 ◽

Cited By ~ 18

Author(s):

Jung-Min Koh ◽

Young-Sun Lee ◽

Chang-Hyun Byun ◽

Eun-Ju Chang ◽

Hyunsoo Kim ◽

...

Keyword(s):

Bone Marrow ◽

Lipoic Acid ◽

Nuclear Factor Κb ◽

Human Bone ◽

Human Bone Marrow ◽

Mouse Bone Marrow ◽

Dependent Manner ◽

Nuclear Factor ◽

Receptor Activator ◽

Dose Dependent

Growing evidence has shown a biochemical link between increased oxidative stress and reduced bone density. Although α-lipoic acid (α-LA) has been shown to act as a thiol antioxidant, its effect on bone cells has not been determined. Using proteomic analysis, we identified six differentially expressed proteins in the conditioned media of α-LA-treated human bone marrow stromal cell line (HS-5). One of these proteins, receptor activator of nuclear factor κB ligand (RANKL), was significantly up-regulated, as confirmed by immunoblotting with anti-RANKL antibody. ELISA showed that α-LA stimulated RANKL production in cellular extracts (membranous RANKL) about 5-fold and in conditioned medium (soluble RANKL) about 23-fold, but had no effect on osteoprotegerin (OPG) secretion. Despite increasing the RANKL/OPG ratio, α-LA showed a dose-dependent suppression of osteoclastogenesis, both in a coculture system of mouse bone marrow cells and osteoblasts and in a mouse bone marrow cell culture system, and reduced bone resorption in a dose-dependent manner. In addition, α-LA-induced soluble RANKL was not inhibited by matrix metalloprotease inhibitors, indicating that soluble RANKL is produced by α-LA without any posttranslational processing. In contrast, α-LA had no significant effect on the proliferation and differentiation of HS-5 cells. These results suggest that α-LA suppresses osteoclastogenesis by directly inhibiting RANKL–RANK mediated signals, not by mediating cellular RANKL production. In addition, our findings indicate that α-LA-induced soluble RANKL is not produced by shedding of membranous RANKL.

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Phytochemical and Biological Screening of Oenothera biennis L. Hydroalcoholic Extract

Biomolecules ◽

10.3390/biom10060818 ◽

2020 ◽

Vol 10 (6) ◽

pp. 818 ◽

Cited By ~ 4

Author(s):

Ramona Fecker ◽

Valentina Buda ◽

Ersilia Alexa ◽

Stefana Avram ◽

Ioana Zinuca Pavel ◽

...

Keyword(s):

Biological Activity ◽

Cell Line ◽

Melanoma Cell ◽

Melanoma Cell Line ◽

Total Phenolic ◽

Dependent Manner ◽

Oenothera Biennis ◽

Hydroalcoholic Extract ◽

Evening Primrose ◽

Anti Inflammatory

Oenothera biennis L. (OB), also commonly known as evening primrose, belongs to the Onagraceae family and has the best studied biological activity of all the members in the family. In therapy, the most frequently used type of extracts are from the aerial part, which are the fatty oils obtained from the seeds and have a wide range of medicinal properties. The aim of this study was to evaluate the phytochemical composition and biological activity of OB hydroalcoholic extract and to provide directions for the antimicrobial effect, antiproliferative and pro-apoptotic potential against A375 melanoma cell line, and anti-angiogenic and anti-inflammatory capacity. The main polyphenols and flavonoids identified were gallic acid, caffeic acid, epicatechin, coumaric acid, ferulic acid, rutin and rosmarinic acid. The total phenolic content was 631.496 µgGAE/mL of extract and the antioxidant activity was 7258.67 μmolTrolox/g of extract. The tested extract had a mild bacteriostatic effect on the tested bacterial strains. It was bactericidal only against Candida spp. and S. aureus. In the set of experimental conditions, the OB extract only manifested significant antiproliferative and pro-apoptotic activity against the A375 human melanoma cell line at the highest tested concentration, namely 60 μg/mL. The migration potential of A375 cells was hampered by the OB extract in a concentration-dependent manner. Furthermore, at the highest tested concentration, the OB extract altered the mitochondrial function in vitro, while reducing the angiogenic reaction, hindering compact tumor formation in the chorioallantoic membrane assay. Moreover, the OB extract elicited an anti-inflammatory effect on the experimental animal model of ear inflammation.

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A Jurkat transcriptional reporter cell line for high-throughput analysis of the Nuclear Factor-κB signaling pathway

New Biotechnology ◽

10.1016/j.nbt.2009.06.982 ◽

2009 ◽

Vol 26 (5) ◽

pp. 244-250 ◽

Cited By ~ 2

Author(s):

Amanda M. Gonzales ◽

Robert A. Orlando

Keyword(s):

Cell Line ◽

Signaling Pathway ◽

High Throughput ◽

Nuclear Factor Κb ◽

Nuclear Factor ◽

Reporter Cell Line ◽

Reporter Cell ◽

High Throughput Analysis ◽

Throughput Analysis ◽

Transcriptional Reporter

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Torque Teno Virus (SANBAN Isolate) ORF2 Protein Suppresses NF-κB Pathways via Interaction with IκB Kinases

Journal of Virology ◽

10.1128/jvi.01101-07 ◽

2007 ◽

Vol 81 (21) ◽

pp. 11917-11924 ◽

Cited By ~ 46

Author(s):

Hong Zheng ◽

Linbai Ye ◽

Xiaonan Fang ◽

Baozong Li ◽

Yuhua Wang ◽

...

Keyword(s):

Western Blot ◽

Nuclear Factor Κb ◽

Torque Teno Virus ◽

Dependent Manner ◽

Nuclear Factor ◽

Innate And Adaptive Immunity ◽

Reading Frame ◽

Orf2 Protein ◽

First Time ◽

Dose Dependent

ABSTRACT Since the first discovery of Torque teno virus (TTV) in 1997, many researchers focused on its epidemiology and transcriptional regulation, but the function of TTV-encoded proteins remained unknown. The function of the TTV open reading frame (ORF) in the nuclear factor κB (NF-κB) pathway has not yet been established. In this study, we found for the first time that the TTV ORF2 protein could suppress NF-κB activity in a dose-dependent manner in the canonical NF-κB pathway. By Western blot analysis, we proved that the TTV ORF2 protein did not alter the level of NF-κB expression but prevented the p50 and p65 subunits from entering the nucleus due to the inhibition of IκBα protein degradation. Further immunoprecipitation assays showed that the TTV ORF2 protein could physically interact with IKKβ as well as IKKα, but not IKKγ. Luciferase assays and Western blot experiments showed that the TTV ORF2 protein could also suppress NF-κB activity in the noncanonical NF-κB pathway and block the activation and translocation of p52. Finally, we found that the TTV ORF2 protein inhibited the transcription of NF-κB-mediated downstream genes (interleukin 6 [IL-6], IL-8, and COX-2) through down-regulation of NF-κB. Together, these data indicate that the TTV ORF2 protein suppresses the canonical and noncanonical NF-κB pathways, suggesting that the TTV ORF2 protein may be involved in regulating the innate and adaptive immunity of organisms, contributing to TTV pathogenesis, and even be related to some diseases.

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