Sa1963 Low Molecular Weight Procyanidins From Grape Seeds Enhance the Impact of 5-Fluorouracil Chemotherapy on Colon Cancer Cells

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.

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A Transcriptomic Insight into the Impact of Colon Cancer Cells on Mast Cells

International Journal of Molecular Sciences ◽

10.3390/ijms20071689 ◽

2019 ◽

Vol 20 (7) ◽

pp. 1689 ◽

Cited By ~ 3

Author(s):

Yingxin Yu ◽

Bart Blokhuis ◽

Johan Garssen ◽

Frank Redegeld

Keyword(s):

Colon Cancer ◽

Mast Cells ◽

Cancer Cells ◽

Colon Cancer Cells ◽

Mhc Molecules ◽

Alternative Approach ◽

Coculture Model ◽

Inducible Genes ◽

The Impact ◽

Cancer Lesion

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.

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Impact of High-Polyphenol Sorghum Varieties on Expression of Selenoproteins in Human Colon Cancer Cells (P06-047-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz031.p06-047-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Ashish Singh ◽

Dmitriy Smolensky ◽

Petra Tsuji

Keyword(s):

Colon Cancer ◽

Mrna Expression ◽

Cancer Cells ◽

Plant Secondary Metabolites ◽

Human Colon ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

Cereal Grain ◽

The Impact ◽

Human Colon Cancer Cells

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).

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The Impact of Extracellular Ca2+ and Nanosecond Electric Pulses on Sensitive and Drug-Resistant Human Breast and Colon Cancer Cells

Cancers ◽

10.3390/cancers13133216 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3216

Author(s):

Julita Kulbacka ◽

Nina Rembiałkowska ◽

Anna Szewczyk ◽

Helena Moreira ◽

Anna Szyjka ◽

...

Keyword(s):

Breast Cancer ◽

Colon Cancer ◽

Drug Resistance ◽

Cancer Cells ◽

Calcium Ions ◽

Colon Cancer Cells ◽

Human Breast ◽

The Impact ◽

Mcf 7 ◽

Resistant Cells

(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.

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Multi-Species Probiotic Modulates Cytokine Production and the Interplay between Immune and Colon Cancer Cells

10.21926/obm.hg.2004053 ◽

2020 ◽

Vol 4 (4) ◽

Author(s):

Meir Djaldetti ◽

Chiya Moshe Leibovitch ◽

Hanna Bessler ◽

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Mononuclear Cells ◽

Cytokine Production ◽

Human Peripheral Blood ◽

Therapeutic Strategies ◽

Colon Cancer Cells ◽

Peripheral Blood Mononuclear ◽

The Impact ◽

Ht 29

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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Yeast-Derived Recombinant Avenanthramides Inhibit Proliferation, Migration and Epithelial Mesenchymal Transition of Colon Cancer Cells

Nutrients ◽

10.3390/nu10091159 ◽

2018 ◽

Vol 10 (9) ◽

pp. 1159 ◽

Cited By ~ 5

Author(s):

Federica Finetti ◽

Andrea Moglia ◽

Irene Schiavo ◽

Sandra Donnini ◽

Giovanni Berta ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Epithelial Mesenchymal Transition ◽

Antioxidant Properties ◽

Colon Cancer Cells ◽

Mesenchymal Transition ◽

Molecular Features ◽

Hydroxyanthranilic Acid ◽

The Impact

Avenanthramides (Avns), polyphenols found exclusively in oats, are emerging as promising therapeutic candidates for the treatment of several human diseases, including colon cancer. By engineering a Saccharomyces cerevisiae strain, we previously produced two novel phenolic compounds, N-(E)-p-coumaroyl-3-hydroxyanthranilic acid (Yeast avenanthramide I, YAvnI) and N-(E)-caffeoyl-3-hydroxyanthranilic acid (Yeast avenanthramide II, YAvnII), which are endowed with a structural similarity to bioactive oat avenanthramides and stronger antioxidant properties. In this study, we evaluated the ability of these yeast-derived recombinant avenanthramides to inhibit major hallmarks of colon cancer cells, including sustained proliferation, migration and epithelial-mesenchymal transition (EMT). Using the human colon adenocarcinoma cell line HT29, we compared the impact of YAvns and natural Avns, including Avn-A and Avn-C, on colon cancer cells by performing MTT, clonogenic, adhesion, migration, and anchorage-independent growth assays, and analyzing the expression of EMT markers. We found that both YAvns and Avns were able to inhibit colon cancer cell growth by increasing the expression of p21, p27 and p53 proteins. However, YAvns resulted more effective than natural compounds in inhibiting cancer cell migration and reverting major molecular features of the EMT process, including the down-regulation of E-cadherin mRNA and protein levels.

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Contribution of FOXC1 to the progression and metastasis and prognosis of human colon cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.636 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 636-636 ◽

Cited By ~ 1

Author(s):

Dawei Li ◽

Qingguo Li ◽

Changhua Zhuo ◽

Ye Xu ◽

Sanjun Cai

Keyword(s):

Colon Cancer ◽

Lymph Node ◽

Cancer Cells ◽

Distant Metastasis ◽

Human Colon ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

The Impact

636 Background: Distant metastasis remains the most common causes to death of colon cancer. Thus it is crucial to identify the molecular markers associated with the progression and metastasis of this disease. Recent evidence for overexpression of FOXC1 in several types of human cancer suggests that it might play a key role in tumor biology. However, the clinical significance of FOXC1 signaling in human colon cancer pathogenesis remains unknown. Methods: We investigated FOXC1 expression in 203 cases of primary colon cancer and matched normal colon tissue and lymph node matastasis in a tissue array. The underlying mechanisms of altered FOXC1 expression and the impact of this altered expression on colon cancer growth and metastasis was explored both in vitro and in vivo. Results: We found elevated expression of FOXC1 protein in cancereous tissue and lymph node metastases than adjacent normal colonic tissues. Overexpression of FOXC1 was associated with higher clinical stage, T stage, lymph node metastasis and presence of distant metastasis. FOXC1 served as an independent prognostic marker whose expression levels correlated with poorer metastasis-free survival (MFS) and poorer overall survival (OS). A Cox proportional hazards model revealed that FOXC1 expression was an independent prognostic factor in multivariate analysis. Experimentally, FOXC1 silencing significantly inhibited the growth and metastasis of colon cancer cells in vitro and in vivo. FOXC1 transcriptionally regulates SNAIL1, contributing to epithelial-to-mesenchymal transition and metastasis in colon cancer cells. Conclusions: Dysregulated expression of FOXC1 may play a critical role in colon cancer progression and metastasis. Thus, FOXC1 may serve as a candidate prognostic biomarker and therapeutically targeted.

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