scholarly journals Does KRAS Play a Role in the Regulation of Colon Cancer Cells-Derived Exosomes?

Biology ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 58
Author(s):  
Shu-Kee Eng ◽  
Ilma Ruzni Imtiaz ◽  
Bey-Hing Goh ◽  
Long Chiau Ming ◽  
Ya-Chee Lim ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Survival ◽  
Recipient Cell ◽  
Cell Types ◽  
Colon Cancer Cells ◽  
Sw480 Cells ◽  
Kras Protein ◽  
High Level ◽  
The Impact

Exosomes are cell-derived nanovesicles, and lately, cancer-derived exosomes have been reported to carry KRAS protein, which contributes to the malignancy of many cancers. In this study, farnesylthiosalicylic acid (FTS) was used to inhibit the activities of mutated KRAS in colon cancer SW480 cells to discover the potential link between KRAS activities and cancer-derived exosomes. We observed that FTS inhibits KRAS activity in SW480 cells, but promotes their exosome production. When the exosomal proteins of SW480 cells were profiled, a total of 435 proteins were identified with 16 of them showing significant changes (greater than or equal to two-fold) in response to FTS treatment. Protein network analysis suggests KRAS inhibition may trigger stress in the cells. In addition, a high level of acetyl-coA synthetase family member 4 protein which plays an important role in colon cancer survival was identified in the exosomes secreted by FTS-treated SW480 cells. The uptake of these exosomes suppresses the growth of some cell types, but in general exosomes from FTS-treated cells enhance the recipient cell survival when compared to that of untreated cells. Together our findings suggest that FTS may trigger stress in SW480 cells, and induce more exosomes secretion as the survival messenger to mitigate the impact of KRAS inhibition in colon cancer cells.

scholarly journals Low Molecular Weight Procyanidins from Grape Seeds Enhance the Impact of 5-Fluorouracil Chemotherapy on Caco-2 Human Colon Cancer Cells

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
Keyword(s):  
Molecular Weight ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Human Colon ◽  
Low Molecular Weight ◽  
Colon Cancer Cells ◽  
Grape Seeds ◽  
Human Colon Cancer ◽  
The Impact ◽  
Human Colon Cancer Cells

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

2014 ◽  
Vol 146 (5) ◽  
pp. S-341 ◽  
Author(s):  
Ker Y. Cheah ◽  
Gordon S. Howarth ◽  
Keren A. Bindon ◽  
James A. Kennedy ◽  
Suzanne Mashtoub ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Low Molecular Weight ◽  
Colon Cancer Cells ◽  
Grape Seeds ◽  
The Impact

scholarly journals miR-188 promotes Oxaliplatin resistances through targeting RASA1 in colon cancer cells

2019 ◽  
Author(s):  
Xijia Zhu ◽  
Xishun Luo ◽  
Zhike Song ◽  
Shiyu Jiang ◽  
Xiangkai Long ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Annexin V ◽  
Luciferase Assay ◽  
Cell Cycle Distribution ◽  
Colon Cancer Cells ◽  
Hoechst 33342 ◽  
Luciferase Activity Assay ◽  
Sw480 Cells

Abstract Background: The chemoresistance of colon cancer cells limits the efficacy of chemotherapy. miR-188 has been shown to be down-regulated in various types of cancer. The aim of this study was to explore the molecular mechanism of miR-188 in drug resistant cancer cells. Materials and methods: we examined the effects of miR-188 on the sensitivity of colon cancer cells to oxaliplatin (OXA) by using SW480/OXA cell line. The target of miR-188 was determined by luciferase activity assay. The cell cycle distribution were detected by flow cytometry. The expression of p21, Hoechst 33342 staining and Annexin V assays were used to detect the cell apoptosis. Results: The expression of miR-188 was significantly increased in SW480/OXA cells compared with SW480 cells. By luciferase assay we found that miR‑188 miRNA binds to RASA1 (Ras GTPase-activating protein 1, also known as p120RasGAP), and overexpression of miR‑188 inhibited RASA1 expression by binding to the 3'-untranslated region of RASA1 mRNA. In addition, suppression of miR‑188 enhanced the chemosensitivity of the oxaliplatin-resistant colon cancer cells. Furthermore, suppression of RASA1 abrogated the increasement of cell apoptosis induced by miR-188 inhibitor, while, overexpression of RASA1 induced cell apoptosis in SW480/OXA cells. Our results suggested that miR-188 played chemoresistant role in colon cancer through regulating RASA1 expression. Conclusion: The findings of our study suggest that target miR-188 is capable of enhancing the chemosensitivity of colon cancer cells by promoting RASA1.

scholarly journals Cortisol and Testosterone Induce Bax and Bcl-2 Gene Expression and Caspases-8 and -9 Activity in Colon Cancer Cells (ht29) and Reduced the Cell Viability

2021 ◽  
Author(s):  
Amin Sarkhosh ◽  
Rahim Ahmadi ◽  
Seyyed Hossein Khatami ◽  
Hadi Ghasemi
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Colorimetric Method ◽  
Caspase 8 ◽  
Activity Levels ◽  
Colon Cancer Cells ◽  
Expression Levels ◽  
Colorectal Cancer Cells ◽  
The Impact

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.

scholarly journals miR-188 promotes Oxaliplatin resistances through targeting RASA1 in colon cancer cells

2020 ◽  
Author(s):  
Xijia Zhu ◽  
Xishun Luo ◽  
Zhike Song ◽  
Shiyu Jiang ◽  
Xiangkai Long ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Annexin V ◽  
Luciferase Assay ◽  
Cell Cycle Distribution ◽  
Colon Cancer Cells ◽  
Hoechst 33342 ◽  
Luciferase Activity Assay ◽  
Sw480 Cells

Abstract Background: One main drawback of chemotherapy application in colon cancer clinically is drug resistance. miR-188-5p has been shown to be down-regulated in various types of cancer. The aim of this study was to explore the molecular mechanism of miR-188-5p in drug resistant cancer cells. Methods: we examined the effects of miR-188-5p on the sensitivity of colon cancer cells to oxaliplatin (OXA) by using SW480/OXA cell line. The target of miR-188-5p was determined by luciferase activity assay. The cell cycle distribution were detected by flow cytometry. The expression of p21, Hoechst 33342 staining and Annexin V assays were used to detect the cell apoptosis. Results: The expression of miR-188-5p was significantly increased in SW480/OXA cells compared with SW480 cells. By luciferase assay we found that miR-188-5p miRNA binds to RASA1 (Ras GTPase-activating protein 1, also known as p120RasGAP), and overexpression of miR-188-5p inhibited RASA1 expression by binding to the 3'-untranslated region of RASA1 mRNA. In addition, suppression of miR-188-5p enhanced the chemosensitivity of the oxaliplatin-resistant colon cancer cells. Furthermore, suppression of RASA1 abrogated the increasement of cell apoptosis induced by miR-188-5p inhibitor, while, overexpression of RASA1 induced cell apoptosis in SW480/OXA cells. Our results suggested that miR-188-5p played chemoresistant role in colon cancer through regulating RASA1 expression. Conclusion: The findings of our study suggest that target miR-188-5p is capable of enhancing the chemosensitivity of colon cancer cells by promoting RASA1.

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

2019 ◽  
Vol 20 (7) ◽  
pp. 1689 ◽  
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.

MiR-125b Inhibits Cell Proliferation and Induces Apoptosis in Human Colon Cancer SW480 Cells via Targeting STAT3

2021 ◽  
Vol 16 ◽  
Author(s):  
Junhe Zhang ◽  
Wenwen Yang ◽  
Yunxi Xiao ◽  
Linlin Shan
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Luciferase Reporter ◽  
Colon Cancer Cells ◽  
Luciferase Reporter Gene ◽  
Luciferase Reporter Gene Assay ◽  
Gene Assay ◽  
Proliferation And Apoptosis ◽  
Sw480 Cells

Background: Colon cancer is one of the most common types of cancer worldwide. Multiple studies have unveiled the key role of microRNAs (miRNAs) in the development of various types of cancer. However, the mechanism of action of miR-125b in the development and progression of colon cancer remains unknown. Objective: In this study, we explored the association of miR-125b and signal transducer and activator of transcription 3 (STAT3) and its role in the proliferation and apoptosis of SW480 colon cancer cells. Methods: The miR-125b expression in NCM460, SW480, HT29, and HCT8 cells was detected using quantitative real-time polymerase chain reaction (qRT-PCR). SW480 cells were transfected with lentiviruses of GFP–miR–125b and GFP–NC to establish a stable miR-125b overexpression colon cancer cell model and a control model. The targeting relationship between miR-125b and STAT3 was analyzed using bioinformatics and verified by the dual-luciferase reporter gene assay. Cell proliferation and apoptosis were assessed using the Cell Counting Kit-8 assay and TUNEL staining. The expression levels of STAT3, Bcl-2, and Bax were analyzed using Western blot analysis. Results: It was found that the relative mRNA expression of miR-125b was decreased in SW480, HT29, and HCT8 cells compared with that in NCM460 cells (P<0.05). The luciferase reporter gene assay confirmed that miR-125b downregulated the STAT3 gene expression (P<0.05). Overexpression of miR-125b inhibited proliferation and promoted apoptosis in SW480 colon cancer cells and was accompanied by upregulated Bax expression and downregulated Bcl-2 expression (P<0.05). Re-expression of STAT3 promoted cell proliferation and inhibited cell apoptosis, whereas Bcl-2 expression increased, and Bax expression decreased (P<0.05). Conclusion: The miR-125b regulates the expression of Bax and Bcl-2 by downregulating the expression of STAT3, thereby inhibiting proliferation and inducing apoptosis of SW480 colon cancer cells.

scholarly journals Activation of P2×7 Receptor Promotes the Invasion and Migration of Colon Cancer Cells via the STAT3 Signaling

2020 ◽  
Vol 8 ◽  
Author(s):  
Wen-jun Zhang ◽  
Ce-gui Hu ◽  
Hong-liang Luo ◽  
Zheng-ming Zhu
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Receptor Activation ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Stat3 Pathway ◽  
Invasion And Migration ◽  
Sw480 Cells ◽  
And Migration

The pathological mechanism of colon cancer is very complicated. Therefore, exploring the molecular basis of the pathogenesis of colon cancer and finding a new therapeutic target has become an urgent problem to be solved in the treatment of colon cancer. ATP plays an important role in regulating the progression of tumor cells. P2 × 7 belongs to ATP ion channel receptor, which is involved in the progression of tumors. In this study, we explored the effect and molecular mechanism of ATP-mediated P2 × 7 receptor on the migration and metastasis of colon cancer cells. The results showed that ATP and BzATP significantly increased the inward current and intracellular calcium concentration of LOVO and SW480 cells, while the use of antagonists (A438079 and AZD9056) could reverse the above phenomenon. We found that ATP promoted the migration and invasion of LOVO and SW480 cells and is dose-dependent on ATP concentration (100–300 μM). Similarly, BzATP (10, 50, and 100 μM) also significantly promoted the migration and invasion of colon cancer cells in a concentration-dependent manner. While P2 × 7 receptor antagonists [A438079 (10 μM), AZD9056 (10 μM)] or P2 × 7 siRNA could significantly inhibit ATP-induced colon cancer cell migration and invasion. Moreover, in vivo experiments showed that ATP-induced activation of P2 × 7 receptor promoted the growth of tumors. Furthermore, P2 × 7 receptor activation down-regulated E-cadherin protein expression and up-regulated MMP-2 mRNA and concentration levels. Knocking down the expression of P2 × 7 receptor could significantly inhibit the increase in the expression of N-cadherin, Vimentin, Zeb1, and Snail induced by ATP. In addition, ATP time-dependently induced the activation of STAT3 via the P2 × 7 receptor, and the STAT3 pathway was required for the ATP-mediated invasion and migration. Our conclusion is that ATP-induced P2 × 7 receptor activation promotes the migration and invasion of colon cancer cells, possibly via the activation of STAT3 pathway. Therefore, the P2 × 7 receptor may be a potential target for the treatment of colon cancer.

scholarly journals Impact of High-Polyphenol Sorghum Varieties on Expression of Selenoproteins in Human Colon Cancer Cells (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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