scholarly journals Increased ENT2 Expression and Its Association With Altered Purine Metabolism in Different Stages of Colorectal Cancer Cell Lines

2022 ◽  
Author(s):  
Safaa M. Naes ◽  
Sharaniza Ab-Rahim ◽  
Musalmah Mazlan ◽  
Nurul Azmir Amir Hashim ◽  
Amirah Abdul Rahman
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Purine Metabolism ◽  
Hypoxanthine Phosphoribosyl Transferase ◽  
Normal Colon ◽  
Colon Cells ◽  
Potential Marker ◽  
Colon Cell ◽  
Colon Cell Line ◽  
Therapeutic Development

Abstract Background Colorectal cancer (CRC) is one of the most prevalent malignant cancers worldwide. Although the purine metabolism pathway is known to be vital for cancer cells survival mechanism, not much is known on ENT2 role in CRC development and its association with purine metabolites. Hence this study is aimed to determine the level of hypoxanthine phosphoribosyl transferase (HPRT), hypoxanthine, uric acid (UA), and the activity of xanthine oxidase (XO) and relate the findings with the ENT2 expression level in different CRC stages. Methods and results Normal colon cell line; CCD-841CoN and a panel of human CRC cell lines; SW480, HCT15 and HCT116, representing different CRC stages; Dukes’ B, C, and D respectively, have been used to measure HPRT, hypoxanthine/xanthine, UA levels and the activity of XO by biochemical assays. The level of ENT2 gene expression was also performed by qRT-PCR. The levels of HPRT, hypoxanthine were significantly higher (P< 0.05), while XO and UA were lower (P< 0.05) in all CRC stages as compared to the normal colon cells. Furthermore, ENT2 expression was found to be increased in all CRC stages. Despite having the highest level of HPRT and hypoxanthine, ENT2 level is lower in Dukes' D when compared to Dukes' B and C. Conclusion The rate of salvage pathway is increased in CRC development as indicated by the elevated levels of HPRT and hypoxanthine in different CRC stages. Increase ENT2 expression implies its importance in assisting hypoxanthine uptake. This step is vital in order to increase DNA synthesis via hypoxanthine recycling. Thus, ENT2 may be a potential marker in therapeutic development.

scholarly journals Metabolomic characterization of colorectal cancer cell lines highlighting stage-specific alterations during cancer progression

Bioimpacts ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 147-156
Author(s):  
Hazwani Mohd Yusof ◽  
Sharaniza Ab-Rahim ◽  
Wan Zurinah Wan Ngah ◽  
Sheila Nathan ◽  
A Rahman A Jamal ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Metabolite Profiling ◽  
Treatment Strategies ◽  
Normal Colon ◽  
Colon Cells ◽  
Colon Cell ◽  
Established Cell ◽  
Stage D

Introduction: Metabolomic studies on various colorectal cancer (CRC) cell lines have improved our understanding of the biochemical events underlying the disease. However, the metabolic profile dynamics associated with different stages of CRC progression is still lacking. Such information can provide further insights into the pathophysiology and progression of the disease that will prove useful in identifying specific targets for drug designing and therapeutics. Thus, our study aims to characterize the metabolite profiles in the established cell lines corresponding to different stages of CRC. Methods: Metabolite profiling of normal colon cell lines (CCD 841 CoN) and CRC cell lines corresponding to different stages, i.e., SW 1116 (stage A), HT 29 and SW 480 (stage B), HCT 15 and DLD-1 (stage C), and HCT 116 (stage D), was carried out using liquid chromatography-mass spectrometry (LC-MS). Mass Profiler Professional and Metaboanalyst 4.0 software were used for statistical and pathway analysis. METLIN database was used for the identification of metabolites. Results: We identified 72 differential metabolites compared between CRC cell lines of all the stages and normal colon cells. Principle component analysis and partial least squares discriminant analysis score plot were used to segregate normal and CRC cells, as well as CRC cells in different stages of the disease. Variable importance in projection score identified unique differential metabolites in CRC cells of the different stages. We identified 7 differential metabolites unique to stage A, 3 in stage B, 5 in stage C, and 5 in stage D. Conclusion: This study highlights the differential metabolite profiling in CRC cell lines corresponding to different stages. The identification of the differential metabolites in CRC cells at individual stages will lead to a better understanding of the pathophysiology of CRC development and progression and, hence, its application in treatment strategies.

scholarly journals Oxidative stress induced by tBHP in human normal colon cells by label free Raman spectroscopy and imaging. The protective role of natural antioxidants in the form of β-carotene

RSC Advances ◽  
2021 ◽  
Vol 11 (27) ◽  
pp. 16419-16434
Author(s):  
B. Brozek-Pluska ◽  
K. Beton
Keyword(s):  
Oxidative Stress ◽  
Natural Antioxidants ◽  
Protective Role ◽  
Label Free ◽  
Normal Colon ◽  
Stress Injury ◽  
Colon Cells ◽  
Colon Cell ◽  
Colon Cell Line ◽  
Β Carotene

The present study aimed to investigate the protective effect of β-carotene on the oxidative stress injury of human normal colon cell line CCD-18Co triggered by tert-butyl hydroperoxide (tBHP).

scholarly journals Antiproliferative Efficacy of N-(3-chloro-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine, DW-8, in Colon Cancer Cells Is Mediated by Intrinsic Apoptosis

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4417
Author(s):  
Rabin Neupane ◽  
Saloni Malla ◽  
Mariam Sami Abou-Dahech ◽  
Swapnaa Balaji ◽  
Shikha Kumari ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Colon Cancer Cells ◽  
Apoptotic Pathway ◽  
Anticancer Efficacy ◽  
Colon Cell ◽  
Ic50 Values ◽  
Induced Apoptosis

A novel series of 4-anilinoquinazoline analogues, DW (1–10), were evaluated for anticancer efficacy in human breast cancer (BT-20) and human colorectal cancer (CRC) cell lines (HCT116, HT29, and SW620). The compound, DW-8, had the highest anticancer efficacy and selectivity in the colorectal cancer cell lines, HCT116, HT29, and SW620, with IC50 values of 8.50 ± 2.53 µM, 5.80 ± 0.92 µM, and 6.15 ± 0.37 µM, respectively, compared to the non-cancerous colon cell line, CRL1459, with an IC50 of 14.05 ± 0.37 µM. The selectivity index of DW-8 was >2-fold in colon cancer cells incubated with vehicle. We further determined the mechanisms of cell death induced by DW-8 in SW620 CRC cancer cells. DW-8 (10 and 30 µM) induced apoptosis by (1) producing cell cycle arrest at the G2 phase; (2) activating the intrinsic apoptotic pathway, as indicated by the activation of caspase-9 and the executioner caspases-3 and 7; (3) nuclear fragmentation and (4) increasing the levels of reactive oxygen species (ROS). Overall, our results suggest that DW-8 may represent a suitable lead for developing novel compounds to treat CRC.

scholarly journals Arabinoxylan-Based Particles: In Vitro Antioxidant Capacity and Cytotoxicity on a Human Colon Cell Line

Medicina ◽  
2019 ◽  
Vol 55 (7) ◽  
pp. 349 ◽  
Author(s):  
Mayra A. Mendez-Encinas ◽  
Elizabeth Carvajal-Millan ◽  
Agustín Rascón-Chu ◽  
Humberto Astiazarán-García ◽  
Dora E. Valencia-Rivera ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Antioxidant Capacity ◽  
Cell Line ◽  
Human Colon ◽  
Colon Cells ◽  
Antioxidant Power ◽  
Human Colon Cell Line ◽  
Colon Cell ◽  
Colon Cell Line

Background and objectives: Arabinoxylans (AX) can gel and exhibit antioxidant capacity. Previous studies have demonstrated the potential application of AX microspheres as colon-targeted drug carriers. However, the cytotoxicity of AX gels has not been investigated so far. Therefore, the aim of the present study was to prepare AX-based particles (AXM) by coaxial electrospraying method and to investigate their antioxidant potential and cytotoxicity on human colon cells. Materials and Methods: The gelation of AX was studied by monitoring the storage (G′) and loss (G′′) moduli. The morphology of AXM was evaluated using optical and scanning electron microscopy (SEM). The in vitro antioxidant activity of AX before and after gelation was measured using the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) methods. In addition, the effect of AX and AXM on the proliferation of human colon cells (CCD 841 CoN) was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: The final G′ and G′′ values for AX gels were 293 and 0.31 Pa, respectively. AXM presented spherical shape and rough surface with a three-dimensional and porous network. The swelling ratio and mesh size of AXM were 35 g water/g AX and 27 nm, respectively. Gelation decreased the antioxidant activity of AX by 61–64 %. AX and AXM did not affect proliferation or show any toxic effect on the normal human colon cell line CCD 841 CoN. Conclusion: The results indicate that AXM could be promising biocompatible materials with antioxidant activity.

scholarly journals Starvation-Induced Differential Virotherapy Using an Oncolytic Measles Vaccine Virus

Viruses ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 614 ◽  
Author(s):  
Gabriel Scheubeck ◽  
Susanne Berchtold ◽  
Irina Smirnow ◽  
Andrea Schenk ◽  
Julia Beil ◽  
...  
Keyword(s):  
Cell Lines ◽  
Vaccine Virus ◽  
Cell Killing ◽  
Measles Vaccine ◽  
Normal Colon ◽  
Short Term ◽  
Normal Cells ◽  
Colon Cells ◽  
Low Serum

Starvation sensitizes tumor cells to chemotherapy while protecting normal cells at the same time, a phenomenon defined as differential stress resistance. In this study, we analyzed if starvation would also increase the oncolytic potential of an oncolytic measles vaccine virus (MeV-GFP) while protecting normal cells against off-target lysis. Human colorectal carcinoma (CRC) cell lines as well as human normal colon cell lines were subjected to various starvation regimes and infected with MeV-GFP. The applied fasting regimes were either short-term (24 h pre-infection) or long-term (24 h pre- plus 96 h post-infection). Cell-killing features of (i) virotherapy, (ii) starvation, as well as (iii) the combination of both were analyzed by cell viability assays and virus growth curves. Remarkably, while long-term low-serum, standard glucose starvation potentiated the efficacy of MeV-mediated cell killing in CRC cells, it was found to be decreased in normal colon cells. Interestingly, viral replication of MeV-GFP in CRC cells was decreased in long-term-starved cells and increased after short-term low-glucose, low-serum starvation. In conclusion, starvation-based virotherapy has the potential to differentially enhance MeV-mediated oncolysis in the context of CRC cancer patients while protecting normal colon cells from unwanted off-target effects.

Immunihistochemical detection of galNAc-T6 to predict survival in patients with colon cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14682-e14682
Author(s):  
Luis Ubillos ◽  
Mariela Rondan ◽  
Edgardo Berriel ◽  
Daniel Mazal ◽  
Enrique Barrios ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Prognostic Marker ◽  
Cell Lines ◽  
Initial Step ◽  
Cancer Tissue ◽  
Normal Colon ◽  
Colon Tissue ◽  
Tissue Samples ◽  
Independent Prognostic Marker ◽  
Colon Cell

e14682 Background: Alterations in the O-glycosylation is one of the most common changes during colon carcinogenesis, which leads to the expression of short O-glycan antigens (Tn, sialyl-Tn, Tk, and core 6). These structures are associated with malignant behavior being actively investigated as targets for immunotherapy. The enzymes of GalNAc-T family regulate the initial step in mucins O-glycosylation and could be responsible for the altered glycosylation observed in cancer. The aim of this work was to evaluate the expression of GalNAc-T6 in colon cancer, and to determine its role as prognostic marker. Methods: We evaluated GalNAc-T6 expression in colon cell lines by immunocytochemistry, and in colon cancer tissue samples by immunohistochemistry using the monoclonal antibody T6.3 developed by us (Berois et al. J Histochem Cytochem. 2006). We analyzed 103 colon cancer samples and 10 normal colon tissues. Results: We found that GalNAc-T6 (usually expressed in normal placenta, trachea, pancreas and brain) is detected in colon cancer cell lines. GalNAc-T6 was also detected by immunohistochemistry in 50.5% of samples with cancer and no expression was found in normal colon tissue. The staining pattern was predominantly cytoplasmic. Multivariate analysis showed that GalNAc-T6 expression is an independent prognostic marker predicting improved survival in patients with positive tumors (p 0.014). Conclusions: GalNAc-T6 could be a new independent prognostic marker to predict better outcome in colon cancer patients.

scholarly journals Potential Antioxidant and Anticancer Activities of Secondary Metabolites of Nostoc linckia Cultivated under Zn and Cu Stress Conditions

Processes ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1972
Author(s):  
Khaled M. A. Ramadan ◽  
Hossam S. El-Beltagi ◽  
Sanaa M. M. Shanab ◽  
Eman A. El-fayoumy ◽  
Emad A. Shalaby ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Cell Viability ◽  
Cell Line ◽  
Cell Lines ◽  
Heavy Metal Stress ◽  
Stress Conditions ◽  
Anticancer Activities ◽  
Nostoc Linckia ◽  
Colon Cell ◽  
Colon Cell Line

The objective of the present study is to determine the antioxidant and anticancer activities of Nostoc linckia extracts cultivated under heavy metal stress conditions (0.44, 0.88, and 1.76 mg/L for zinc and 0.158, 0.316, 0.632 mg/L for copper). Phycobiliprotein, phenolic compounds, flavonoids, and tannins were measured. Active ingredients of extracts were evaluated by GC-mass spectroscopy. The obtained results revealed that higher zinc and copper concentrations showed growth inhibition while 0.22 mg/L (Zn) and 0.079 mg/L (Cu) enhanced growth, reaching its maximum on the 25th day. Increases in catalase, lipids peroxidation, and antioxidants, as well as tannins and flavonoids, have been induced by integration of 0.88 mg/L (Zn) and 0.316 mg/L (Cu). Elevation of Zn concentration induced augmentation of antioxidant activity of crude extract (DPPH or ABTS), with superior activity at 0.44 mg/L zinc concentration (81.22%). The anticancer activity of Nostoc linckia extract (0.44 mg/L Zn) tested against four cancer cell lines: A549, Hela, HCT 116, and MCF-7. The extract at 500 µg/mL appeared the lowest cell viability of tested cell lines. The promising extract (0.44 mg/L Zn) recorded the lowest cell viability of 25.57% in cervical cell line, 29.74% in breast cell line, 33.10% in lung cell line and 34.53% in the colon cell line. The antioxidant active extract showed significant stability against pH with attributed increase in antioxidant activity in the range between 8–12. The extract can be used effectively as a natural antioxidant and anticancer after progressive testing.

Involvement of ppGalNAc-T6, a new colon cancer marker, in the molecular basis of simple mucin-type O-glycosylated antigen expression

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15060-e15060
Author(s):  
L. Ubillos ◽  
N. Berois ◽  
D. Mazal ◽  
V. Braña ◽  
C. Yacoel ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Lines ◽  
Molecular Basis ◽  
Antigen Expression ◽  
Initial Step ◽  
Enzyme Expression ◽  
Normal Colon ◽  
Abnormal Expression ◽  
Colon Cell ◽  
Sialyl Tn

e15060 Background: Abnormal O-glycosylation is one of the most common changes during colon carcinogenesis, leading to the expression of short truncated O-glycan antigens (such as Tn, sialyl-Tn, Tk, and core 6). These structures which are related with the malignant behavior are actively investigated as immunotherapeutic targets. The ppGalNAc-T family enzymes regulate the initial step of mucin O-glycosylation and could be responsible for the altered glycosylation observed in cancer. The objective of this work was to describe the abnormal expression of ppGalNAc-Ts in colon cancer comparing its relationship with incomplete O- glycosylated antigens. Methods: We studied the gene expression of ppGalNAc-Ts in colon cell lines by RT-PCR assays. Using immunohistochemistry we determined ppGalNAc-T6, Tn, sialyl-Tn, Tk, and core 6 expression in 64 colon cancer samples and in 10 normal colon tissues. Results: We found that ppGalNAc-T6 (an enzyme usually restricted to normal placenta, trachea, brain, and pancreas) is expressed by colon cancer cell lines. Using immunohistochemistry we detected ppGalNAc-T6 in 70.3% of cancer samples with no staining in normal colon tissues. Staining pattern was predominantly cytoplasmatic. Staining of Tn, STn, core 6 and Tk antigens was observed in 87,5%, 79,6%, 76,5% and 68.7% of tumors, respectively. We observed a statistically significant relationship between the enzyme expression and Tn antigen (p=0.009) and core 6 (p=0.001). No relationship was observed between the enzyme expression and sialyl-Tn (p = 0.406) and Tk (p= 0.18) antigens. Conclusions: ppGalNac-T6 is a new tumor marker for colon cancer and its expression is related with the accumulation of two O-glycosylated antigens such as Tn and core 6. This is the first evidence in human tissues suggesting that the abnormal expression of a ppGalNac transferase could be in the molecular basis of aberrant O-glycosylated antigens accumulation in cancer. No significant financial relationships to disclose.

scholarly journals Therapeutic potential of FLANC, a novel primate-specific long non-coding RNA in colorectal cancer

Gut ◽  
2020 ◽  
Vol 69 (10) ◽  
pp. 1818-1831 ◽  
Author(s):  
Martin Pichler ◽  
Cristian Rodriguez-Aguayo ◽  
Su Youn Nam ◽  
Mihnea Paul Dragomir ◽  
Recep Bayraktar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Potential ◽  
Cellular Growth ◽  
Normal Colon ◽  
Colon Cells ◽  
In Vivo Models ◽  
Non Coding Rna ◽  
Long Non Coding Rna

ObjectiveTo investigate the function of a novel primate-specific long non-coding RNA (lncRNA), named FLANC, based on its genomic location (co-localised with a pyknon motif), and to characterise its potential as a biomarker and therapeutic target.DesignFLANC expression was analysed in 349 tumours from four cohorts and correlated to clinical data. In a series of multiple in vitro and in vivo models and molecular analyses, we characterised the fundamental biological roles of this lncRNA. We further explored the therapeutic potential of targeting FLANC in a mouse model of colorectal cancer (CRC) metastases.ResultsFLANC, a primate-specific lncRNA feebly expressed in normal colon cells, was significantly upregulated in cancer cells compared with normal colon samples in two independent cohorts. High levels of FLANC were associated with poor survival in two additional independent CRC patient cohorts. Both in vitro and in vivo experiments demonstrated that the modulation of FLANC expression influenced cellular growth, apoptosis, migration, angiogenesis and metastases formation ability of CRC cells. In vivo pharmacological targeting of FLANC by administration of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine nanoparticles loaded with a specific small interfering RNA, induced significant decrease in metastases, without evident tissue toxicity or pro-inflammatory effects. Mechanistically, FLANC upregulated and prolonged the half-life of phosphorylated STAT3, inducing the overexpression of VEGFA, a key regulator of angiogenesis.ConclusionsBased on our findings, we discovered, FLANC as a novel primate-specific lncRNA that is highly upregulated in CRC cells and regulates metastases formation. Targeting primate-specific transcripts such as FLANC may represent a novel and low toxic therapeutic strategy for the treatment of patients.

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