scholarly journals Lycium barbarum Polysaccharide Promotes Maturation of Dendritic Cell via Notch Signaling and Strengthens Dendritic Cell Mediated T Lymphocyte Cytotoxicity on Colon Cancer Cell CT26-WT

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Wei Wang ◽  
Mingxing Liu ◽  
Yang Wang ◽  
Tao Yang ◽  
Dongsheng Li ◽  
...  

Lycium barbarum polysaccharide (LBP) is the major function component of Lycium barbarum L. and has been previously reported to induce the phenotypic and functional maturation of dendritic cells (DCs) as well as activating T lymphocytes. In the current study, the immunologic cytotoxicity promoting effect of LBP was assessed and the underlying mechanism was explored. The impact of LBP on the phenotype, maturation, and immunogenicity of DCs was assessed. The activity of Notch pathway which is involved in the regulation of LBP on DCs was detected. Afterwards, the influence of LBP on cytotoxicity of DC-mediated cytotoxicity T lymphocytes (CTLs) to CT26-WT colon cancer cells was further assessed. Administration of LBP induced the phenotypic and functional maturation of DCs. After being subjected to LBP, the expression of Notch and Jagged and Notch targets Hes1 and Hes5 was all upregulated. The cytotoxicity of DC-mediated CTLs was strengthened by administration of LBP. Additionally, cytotoxicity of DC-mediated CTLs on CT26-WT colon cancer cells also increased with effector-target ratio. In conclusion, LBP could induce the phenotypic and functional maturation of DCs via Notch signaling and promote the cytotoxicity of DC-mediated CTLs, which could be employed as a promising adjuvant for cancer immunotherapy.

PLoS ONE ◽  
2014 ◽  
Vol 9 (6) ◽  
pp. e98921 ◽  
Author(s):  
Ker Y. Cheah ◽  
Gordon S. Howarth ◽  
Keren A. Bindon ◽  
James A. Kennedy ◽  
Susan E. P. Bastian

2017 ◽  
Vol 38 (1) ◽  
pp. 561-568 ◽  
Author(s):  
Carolina V. De Almeida ◽  
Jofer A. Zamame ◽  
Graziela G. Romagnoli ◽  
Cecilia P. Rodrigues ◽  
Marianna B. Magalhães ◽  
...  

2014 ◽  
Vol 146 (5) ◽  
pp. S-341 ◽  
Author(s):  
Ker Y. Cheah ◽  
Gordon S. Howarth ◽  
Keren A. Bindon ◽  
James A. Kennedy ◽  
Suzanne Mashtoub ◽  
...  

2021 ◽  
Author(s):  
Amin Sarkhosh ◽  
Rahim Ahmadi ◽  
Seyyed Hossein Khatami ◽  
Hadi Ghasemi

Abstract Cortisol and testosterone can inhibit the proliferation of colorectal cancer cells. Cortisol may augment the anti-cancer activity of testosterone in colorectal cancer cells. This research aimed to assess the impact of cortisol and testosterone on the viability of colon cancer cells (HTCs). The cytotoxic effects of cortisol and testosterone were evaluated using the MTT assay. Bax and Bcl-2 expression levels were determined using real-time PCR. The colorimetric method was used to assess the activity of caspase-8 and -9 enzymes. The expression levels of Bax and Bcl-2 genes significantly increased (p<0.001), as well as the activity levels of caspase-8 and -9, were elevated (p<0.001). Testosterone may exert cytotoxic activity in colon cancer cells in the presence of cortisol, and cortisol and testosterone cotreatment may contribute to the elevated Bax and Bcl-2 genes expression and caspase 8 and 9 activity enhancement in colorectal cancer cells.


2019 ◽  
Vol 20 (7) ◽  
pp. 1689 ◽  
Author(s):  
Yingxin Yu ◽  
Bart Blokhuis ◽  
Johan Garssen ◽  
Frank Redegeld

Mast cells (MCs) are one of the first immune cells recruited to a tumor. It is well recognized that MCs accumulate in colon cancer lesion and their density is associated with the clinical outcomes. However, the molecular mechanism of how colon cancer cells may modify MC function is still unclear. In this study, primary human MCs were generated from CD34+ progenitor cells and a 3D coculture model was developed to study the interplay between colon cancer cells and MCs. By comparing the transcriptomic profile of colon cancer-cocultured MCs versus control MCs, we identified a number of deregulated genes, such as MMP-2, VEGF-A, PDGF-A, COX2, NOTCH1 and ISG15, which contribute to the enrichment of cancer-related pathways. Intriguingly, pre-stimulation with a TLR2 agonist prior to colon cancer coculture induced upregulation of multiple interferon-inducible genes as well as MHC molecules in MCs. Our study provides an alternative approach to study the influence of colon cancer on MCs. The transcriptome signature of colon cancer-cocultured MCs may potentially reflect the mechanism of how colon cancer cells educate MCs to become pro-tumorigenic in the initial phase and how a subsequent inflammatory signal—e.g., TLR2 ligands—may modify their responses in the cancer milieu.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Ashish Singh ◽  
Dmitriy Smolensky ◽  
Petra Tsuji

Abstract Objectives Plant secondary metabolites, such as polyphenols, are found in many fruits, grains, and vegetables, and are thus a part of normal human diet. One such food is sorghum (Sorghum bicolor), a cereal grain that contains varying concentrations of polyphenols. Many polyphenols have been implicated in the regulation of colon cancer through modulating the antioxidant defense, which includes some of the major selenoproteins, e.g., thioredoxin reductases (TXNRD) and glutathione peroxidases (GPX). However, because such redox-active enzymes have been shown to be involved in both cancer prevention and promotion, the goal of our study is to assess the impact of high-polyphenol sorghum extracts on the expression of selenoproteins. Methods Human colon cancer cells (HT29, HCT116) were incubated with 1.25 mg high-polyphenol sorghum bran extract per mL medium for 48 h. RNA was extracted with Trizol/Chloroform, and reverse-transcribed to cDNA. mRNA expression of selenoproteins was quantitated using qPCR, normalized to GAPDH, and analyzed using GraphPad Prism. Protein lysates will be used for Western blotting and catalytic activity assays. Results Compared to solvent control, incubation of human colon cancer cells with high-polyphenol sorghum extracts for 48 h moderately impacted mRNA expression of investigated selenoproteins. One of the extracts resulted in a nearly doubled GPX1 mRNA expression in HCT116 cells (p = 0.08), whereas preliminary results suggest that TXNRD1 expression may be lowered. Conclusions High-polyphenol varieties of sorghum may affect selenoprotein expression. Further investigations involving both shorter and longer-term incubation times, as well as effects on protein expression and activity will help elucidate the effects of these new sorghum varieties on selenoprotein expression important in prevention and promotion of colon cancer. Funding Sources Financial support was provided by Towson University's Fisher College of Science and Mathematics (P. Tsuji) and the USDA (D. Smolensky).


2010 ◽  
Vol 28 (1) ◽  
pp. 121-126 ◽  
Author(s):  
Fang Mao ◽  
Bingxiu Xiao ◽  
Zhen Jiang ◽  
Junwei Zhao ◽  
Xia Huang ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3216
Author(s):  
Julita Kulbacka ◽  
Nina Rembiałkowska ◽  
Anna Szewczyk ◽  
Helena Moreira ◽  
Anna Szyjka ◽  
...  

(1) Background: Calcium electroporation (CaEP) is based on the application of electrical pulses to permeabilize cells (electroporation) and allow cytotoxic doses of calcium to enter the cell. (2) Methods: In this work, we have used doxorubicin-resistant (DX) and non-resistant models of human breast cancer (MCF-7/DX, MCF-7/WT) and colon cancer cells (LoVo, LoVo/DX), and investigated the susceptibility of the cells to extracellular Ca2+ and electric fields in the 20 ns–900 ns pulse duration range. (3) Results: We have observed that colon cancer cells were less susceptible to PEF than breast cancer cells. An extracellular Ca2+ (2 mM) with PEF was more disruptive for DX-resistant cells. The expression of glycoprotein P (MDR1, P-gp) as a drug resistance marker was detected by the immunofluorescent (CLSM) method and rhodamine-123 efflux as an MDR1 activity. MDR1 expression was not significantly modified by nanosecond electroporation in multidrug-resistant cells, but a combination with calcium ions significantly inhibited MDR1 activity and cell viability. (4) Conclusions: We believe that PEF with calcium ions can reduce drug resistance by inhibiting drug efflux activity. This phenomenon of MDR mechanism disruption seems promising in anticancer protocols.


2020 ◽  
Vol 4 (4) ◽  
Author(s):  
Meir Djaldetti ◽  
Chiya Moshe Leibovitch ◽  
Hanna Bessler ◽  

The current study aimed to investigate the effect of a multi-species probiotic (MSP) on cytokine production by human peripheral blood mononuclear cells (PBMCs) and their immune dialogue with HT-29 colon cancer cells. PBMCs were incubated with MSP and their effect on cell proliferation and TNFα, IL-1β, IL-2, IL-6, IFNγ, IL-10, and IL-1ra production was evaluated. The impact of MSP on the cytokine production by PBMC stimulated by HT-29 cells was detected. Not-stimulated PBMC incubated with MSP showed increased production of TNFα, IL-1β, IL-6, and IL-10, but no change in IL-6, IFNγ, and IL-1ra. The stimulatory effect of MSP on lipopolysaccharide (LPS)-promoted PBMC was less pronounced for TNFα, IL-1β, and IFNγ, and the IL-6 production was decreased; phorbol 12-myristate 13- acetate (PMA)-induced IL-2 and IFNγ secretion was inhibited. The addition of MSP to co-cultures of PBMC and HT-29 cancer cells caused a remarkable increase in TNFα and IL-1β secretion, with no change in remaining cytokines. The multi-species probiotics modulated cytokine production by PBMC and affected the cross-talk between PBMC and HT-29 cancer cells. We conclude that probiotics may serve as supplements to the therapeutic strategies applied for the treatment of chronic inflammatory and malignant diseases, especially colorectal cancers.


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