Human fetal colon cells and colon cancer cells respond differently to butyrate and PUFAs

2009 ◽  
Vol 53 (S1) ◽  
pp. S102-S113 ◽  
Author(s):  
Jiřina Hofmanová ◽  
Alena Vaculová ◽  
Zuzana Koubková ◽  
Martina Hýžd'alová ◽  
Alois Kozubík
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Colon Cancer Cells ◽  
Colon Cells

scholarly journals Destruxin B Suppresses Drug-Resistant Colon Tumorigenesis and Stemness Is Associated with the Upregulation of miR-214 and Downregulation of mTOR/β-Catenin Pathway

Cancers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 353 ◽  
Author(s):  
Szu-Yuan Wu ◽  
Yan-Jiun Huang ◽  
Yew-Min Tzeng ◽  
Chi-Ying Huang ◽  
Michael Hsiao ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Side Population ◽  
Colon Cancer Cells ◽  
Cancer Stemness ◽  
Colon Cells ◽  
Colon Tumorigenesis ◽  
Tumor Sphere ◽  
Sphere Formation

Background: Drug resistance represents a major challenge for treating patients with colon cancer. Accumulating evidence suggests that Insulin-like growth factor (IGF)-associated signaling promotes colon tumorigenesis and cancer stemness. Therefore, the identification of agents, which can disrupt cancer stemness signaling, may provide improved therapeutic efficacy. Methods: Mimicking the tumor microenvironment, we treated colon cancer cells with exogenous IGF1. The increased stemness of IGF1-cultured cells was determined by ALDH1 activity, side-population, tumor sphere formation assays. Destruxin B (DB) was evaluated for its anti-tumorigenic and stemness properties using cellular viability, colony-formation tests. The mimic and inhibitor of miR-214 were used to treat colon cancer cells to show its functional association to DB treatment. In vivo mouse models were used to evaluate DB’s ability to suppress colon tumor-initiating ability and growth inhibitory function. Results: IGF1-cultured colon cancer cells showed a significant increase in 5-FU resistance and enhanced stemness properties, including an increased percentage of ALDH1+, side-population cells, tumor sphere generation in vitro, and increased tumor initiation in vivo. In support, using public databases showed that increased IGF1 expression was significantly associated with a poorer prognosis in patients with colon cancer. DB, a hexadepsipeptide mycotoxin, was able to suppress colon tumorigenic phenotypes, including colony and sphere formation. The sequential treatment of DB, followed by 5-FU, synergistically inhibited the viability of colon cancer cells. In vivo studies showed that DB suppressed the tumorigenesis by 5-FU resistant colon cells, and in a greater degree when combined with 5-FU. Mechanistically, DB treatment was associated with decreased the mammalian target of rapamycin (mTOR) and β-catenin expression and an increased miR-214 level. Conclusion: We provided evidence of DB as a potential therapeutic agent for overcoming 5-FU resistance induced by IGF1, and suppressing cancer stem-like properties in association with miR-214 regulation. Further investigation is warranted for its translation to clinical application.

scholarly journals CHK Methylation Is Elevated in Colon Cancer Cells and Contributes to the Oncogenic Properties

2021 ◽  
Vol 9 ◽  
Author(s):  
Shudong Zhu ◽  
Yan Zhu ◽  
Qiuwen Wang ◽  
Yi Zhang ◽  
Xialing Guo
Keyword(s):  
Dna Methylation ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Human Colon ◽  
Dna Methyltransferases ◽  
Colon Cancer Cells ◽  
Normal Colon ◽  
Human Colon Cancer ◽  
Colon Cells ◽  
Matrigel Invasion

Src is an important oncogene that plays key roles in multiple signal transduction pathways. Csk-homologous kinase (CHK) is a kinase whose molecular roles are largely uncharacterized. We previously reported expression of CHK in normal human colon cells, and decreased levels of CHK protein in colon cancer cells leads to the activation of Src (Zhu et al., 2008). However, how CHK protein expression is downregulated in colon cancer cells has been unknown. We report herein that CHK mRNA was decreased in colon cancer cells as compared to normal colon cells, and similarly in human tissues of normal colon and colon cancer. Increased levels of DNA methylation at promotor CpG islands of CHK gene were observed in colon cancer cells and human colon cancer tissues as compared to their normal healthy counterparts. Increased levels of DNA methyltransferases (DNMTs) were also observed in colon cancer cells and tissues. DNA methylation and decreased expression of CHK mRNA were inhibited by DNMT inhibitor 5-Aza-CdR. Cell proliferation, colony growth, wound healing, and Matrigel invasion were all decreased in the presence of 5-Aza-CdR. These results suggest that increased levels of DNA methylation, possibly induced by enhanced levels of DNMT, leads to decreased expression of CHK mRNA and CHK protein, promoting increased oncogenic properties in colon cancer cells.

scholarly journals A Nudibranch Marine Extract Selectively Chemosensitizes Colorectal Cancer Cells by Inducing ROS-Mediated Endoplasmic Reticulum Stress

2021 ◽  
Vol 12 ◽  
Author(s):  
Verónica Ruiz-Torres ◽  
Nicholas Forsythe ◽  
Almudena Pérez-Sánchez ◽  
Sandra Van Schaeybroeck ◽  
Enrique Barrajón-Catalán ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Cancer Cells ◽  
Human Colon ◽  
Resistance Mechanisms ◽  
Colon Cancer Cells ◽  
Colon Cells ◽  
Lower Effect ◽  
The Unfolded Protein Response

The present study shows the putative antiproliferative mechanism of action of the previously analytically characterized nudibranch extract ( Dolabella auricularia, NB) and its different effects in colon cancer cells vs. nontumor colon cells. NB extract increased the accumulation of reactive oxygen species (ROS) and increased endoplasmic reticulum (ER) stress via stimulation of the unfolded protein response. Stress scavengers, N-acetylcysteine (NAC) and 4-phenylbutyric acid (4-PBA), decreased the stress induced by NB. The results showed that NB extract increased ER stress through overproduction of ROS in superinvasive colon cancer cells, decreased their resistance threshold, and produced a nonreturn level of ER stress, causing DNA damage and cell cycle arrest, which prevented them from achieving hyperproliferative capacity and migrating to and invading other tissues. On the contrary, NB extract had a considerably lower effect on nontumor human colon cells, suggesting a selective effect related to stress balance homeostasis. In conclusion, our results confirm that the growth and malignancy of colon cancer cells can be decreased by marine compounds through the modification of one of the most potent resistance mechanisms present in tumor cells; this characteristic differentiates cancer cells from nontumor cells in terms of stress balance.

scholarly journals GDF15 Repression Contributes to 5-Fluorouracil Resistance in Human Colon Cancer by Regulating Epithelial-Mesenchymal Transition and Apoptosis

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Bin Wang ◽  
Nina Ma ◽  
Xixi Zheng ◽  
Xiao Li ◽  
Xiao Ma ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Growth Inhibition Assay ◽  
Colon Cells ◽  
Mesenchymal Transition

Chemotherapy based on 5-fluorouracil (5-FU) is the standard approach for colon cancer treatment, and resistance to 5-FU is a significant obstacle in the clinical treatment of colon cancer. However, the mechanisms underlying 5-FU resistance in colon cancer cells remain largely unknown. This study aimed at determining whether 5-FU-resistant colon cancer cells undergo epithelial-mesenchymal transition (EMT) and apoptosis and the role of GDF15—a member of the transforming growth factor β/bone morphogenetic protein super family and a protein known to be involved in cancer progression—in the regulation of EMT and apoptosis of these cells, along with the underlying mechanisms. In vitro apoptosis detection assay, growth inhibition assay, transwell, and wound healing experiments revealed that 5-FU-resistant colon cancer cells possessed enhanced EMT and antiapoptotic ability. These cells also showed a stronger tendency to proliferate and metastasize in vivo. Quantitative reverse transcription-PCR and western blotting revealed that 5-FU-resistant colon cancer cells expressed lower levels of growth differentiation factor 15 (GDF15) than did 5-FU-sensitive colon cancer cells. Moreover, the transient GDF15 overexpression resensitized 5-FU-resistant colon cells to 5-FU. Collectively, these findings indicate the mechanism underlying the 5-FU resistance of colon cancer cells and provide new therapeutic targets for improving the prognosis of colon cancer patients.

scholarly journals Release of cell surface proteoglycans from differentiating colon cells proceeds by cleavage of lipophilic anchor peptides

1992 ◽  
Vol 287 (1) ◽  
pp. 131-140 ◽  
Author(s):  
J A McBain ◽  
G C Mueller
Keyword(s):  
Colon Cancer ◽  
Cell Surface ◽  
Cancer Cells ◽  
Heparan Sulphate ◽  
Buoyant Density ◽  
Terminal Differentiation ◽  
Proteinase K ◽  
Colon Cancer Cells ◽  
Colon Cells ◽  
Core Proteins

Heparan sulphate proteoglycans are rapidly released from VACO 10MS colon cancer cells that are triggered with phorbol esters to undergo terminal differentiation. This lag-free temperature-sensitive process is correlated with a conversion of the lipophilic proteoglycans of the cell surface into non-lipophilic proteoglycans that accumulate in the culture medium. The released proteoglycans are very similar to their lipophilic precursors in size, buoyant density and glycosaminoglycan characteristics; however, they exhibit slightly smaller core proteins after chemical and enzymic deglycosylation. The lipophilicity of the larger-sized core proteins of the cell-associated proteoglycans is also correlated with the presence of an easily iodinatable domain; this domain is missing in the released proteoglycans. Exogenous proteases (i.e. chymotrypsin, V8, trypsin and proteinase K) readily cleave this segment from the larger protease-resistant region of the proteoglycan structure. It is also released intact by treatment of the isolated proteoglycans with methanolic HCl. This component appears to be peptide in character, in that proteases readily degrade it and release iodotyrosines when the precursor has been iodinated. No evidence for the presence of covalently attached fatty acids in the cell-associated proteoglycans was found. These results are consistent with the hypothesis that the altered proteoglycan metabolism that is associated with the phorbol-ester-induced terminal differentiation of certain human colon cancer cells ensues upon the activation of a membrane-localized protease that cleaves a lipophilic anchor segment from the cell surface proteoglycans.

scholarly journals Mixtures of SCFA, composed according to physiologically available concentrations in the gut lumen, modulate histone acetylation in human HT29 colon cancer cells

2006 ◽  
Vol 96 (5) ◽  
pp. 803-810 ◽  
Author(s):  
Jeannette Kiefer ◽  
Gabriele Beyer-Sehlmeyer ◽  
Beatrice L. Pool-Zobel
Keyword(s):  
Colon Cancer ◽  
Histone Acetylation ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Biological Activities ◽  
Biological Effects ◽  
Colon Cancer Cells ◽  
Colon Cells ◽  
Positive Effects ◽  
Gut Fermentation

Intake of fibre has beneficial properties on gut health. Butyrate, a product of bacterial gut fermentation, is thought to contribute to positive effects by retarding growth and enhancing apoptosis of tumour cells. One mechanism is seen in its capacity to modulate histone acetylation and thereby transcriptional activity of genes. Next to butyrate, propionate and acetate are also major products of gut fermentation and together they may exert different potencies of cellular effects than butyrate alone. Since virtually nothing is known on combination effects by SCFA mixtures, here we had the aim to assess how physiological relevant concentrations and mixtures of SCFA modulate histone acetylation in human colon cells. HT29 colon cancer cells were incubated with mixtures of butyrate, acetate and propionate and with the individual compounds as controls. Histone acetylation was determined with acid-urea gel electrophoresis and immunoblotting. Acetylated histones slowly increased over 24 h and persisted up to 72 h in butyrate-treated HT29 cells. Butyrate (5–40 mm) and propionate (20–40 mm) enhanced histone acetylation significantly after 24 h incubation, whereas acetate (2·5–80 mm) was ineffective. Mixtures of these SCFA also modulated histone acetylation, mainly due to additive effects of butyrate and propionate, but not due to acetate. In conclusion, physiological concentrations of propionate together with butyrate could have more profound biological activities than generally assumed. Together, these SCFA could possibly mediate important processes related to an altered transcriptional gene activation and thus contribute to biological effects possibly related to cancer progression or prevention.

Leptin is a growth factor for human colon cancer cells

2001 ◽  
Vol 120 (5) ◽  
pp. A493-A493
Author(s):  
J HARDWICK ◽  
G VANDENBRINK ◽  
S VANDEVENTER ◽  
M PEPPELENBOSCH
Keyword(s):  
Colon Cancer ◽  
Growth Factor ◽  
Cancer Cells ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Human Colon Cancer Cells
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