scholarly journals Curcumin Analogs, PGV-1 and CCA-1.1 Exhibit Anti-migratory Effects and Suppress MMP9 Expression on WiDr Cells

2021 ◽  
Vol 13 (3) ◽  
pp. 271-80
Author(s):  
Febri Wulandari ◽  
Muthi' Ikawati ◽  
Mitsunori Kirihata ◽  
Jun-Ya Kato ◽  
Edy Meiyanto
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Expression Profiles ◽  
Gelatin Zymography ◽  
Anticancer Activities ◽  
Curcumin Analog ◽  
Migration Assay ◽  
Migratory Activity ◽  
Mmp9 Expression

BACKGROUND: Colon cancer is still a crucial concern in the development of chemotherapeutic drugs due to the drug resistance phenomenon and various side effects to patients. One of the newest compound that show anticancer activities against several cancer cells, Chemoprevention Curcumin Analog 1 (CCA-1.1), has increasingly been explored to overcome the limitation of conventional drugs.METHODS: We evaluated the anti-migratory effect of CCA-1.1 and Pentagamavunone-1 (PGV-1) by using WiDr colon cancer cells. The expression profiles of Tumor Protein 53 (TP53) and Matrix Metalloproteinase-9 (MMP9) in colon cancer were obtained from the UALCAN database. Survival outcomes of TP53 and MMP9 in colon cancer patients were analyzed using the Kaplan-Meier method. We used 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT), scratch wound healing, and gelatin zymography assays to observe the cytotoxic effect, anti-migratory activity, and MMP9 expression, respectively, in CCA-1.1 or PGV-1-treated cells.RESULTS: Level of MMP9 was found significantly overexpressed in the primary tumor and metastasis nodal, while TP53 mutation sample types were observed and influenced the survival outcome in colon cancer patients. CCA-1.1 and PGV-1 exhibited strong cytotoxic activity after 24 and 48 h treatment against WiDr cells. The migration assay demonstrated that PGV-1 and CCA-1.1 at 1 mM inhibited cell migration up to 40% after 48 h in single and combination with doxorubicin. The MMP9 expression was significantly inhibited by 0.5 mM CCA-1.1.CONCLUSION: This study emphasizes that the anti-migratory effect of CCA-1.1 is better than PGV-1 via MMP9 suppression on WiDr. Thus, CCA-1.1 is prominent to be developed as an anti-metastatic agent.KEYWORDS: chemopreventive curcumin analog 1.1 (CCA-1.1), PGV-1, WiDr cells, anti-migration, MMP9

scholarly journals Screening of Differentiation-Specific Molecular Biomarkers for Colon Cancer

2018 ◽  
Vol 46 (6) ◽  
pp. 2543-2550 ◽  
Author(s):  
Lu Qi ◽  
Yanqing Ding
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Molecular Markers ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Roc Curve ◽  
Expression Profiles ◽  
Tissue Specific ◽  
Specificity And Sensitivity ◽  
Cancer Tissues

Background/Aims: Owing to the lack of effective molecular markers to evaluate colon cancer differentiation grade, screening of effective molecular markers for the diagnosis and treatment of colon cancer is of great significance. This study is a screening study for molecular markers related to the differentiation of colon using the tissue-specific genes of colon. Methods: This study compared the expression profiles of colon cancer at various differentiation grades and screened the down-regulated genes associated with decreased differentiation. IL22RA1 gene was derived from the intersection of obtained gene and colon tissue-specific genes. We used DriverDB and The Human Protein Atlas to analyze the expression level of IL22RA1 in various tissue cells, also used Kaplan-Meier method to analyze the correlation between IL22RA1 and the survival of colon cancer patients, and then used the ROC curve to analyze the specificity and sensitivity of IL22RA1 diagnosis of differentiated colon cancer. Results: We found that IL22RA1 gene expression was progressively down-regulated in high-differentiated, moderate-differentiated, low-differentiated, and undifferentiated colon cancer tissues. Both RNA and protein levels of IL22RA1 were higher in colon tissues and colon cancer tissues than in other normal and cancer tissues. Comparison of IL22RA1 expression in different cancer cells found that IL22RA1 expression was significantly higher in CACO-2 colon cancer cells than in other cancer cells. Survival analysis showed that IL22RA1 gene expression was positively correlated with the overall survival rate of colon cancer patients (P=0.0224). ROC curve analysis revealed that IL22RA1 expression had good specificity and sensitivity to stage II colon cancer. Conclusion: These findings suggest that IL22RA1 serves as a specific molecular marker for the differentiation of colon cancer.

scholarly journals Water Soluble Pleurotus ostreatus Polysaccharide Down-Regulates the Expression of MMP-2 and MMP-9 in Caco-2 Cells

2013 ◽  
Vol 41 (2) ◽  
pp. 553
Author(s):  
Sabina COJOCARU ◽  
Mihaela RADU ◽  
Liviu Gabriel BODEA ◽  
Mirela Mihaela CIMPEANU ◽  
Gogu GHEORGHITA ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Protein Complexes ◽  
Gelatin Zymography ◽  
Water Soluble ◽  
Colon Cancer Cells ◽  
Sod Activity ◽  
Kinetic Measurements ◽  
The Third

Many polysaccharides and polysaccharide-protein complexes isolated from mushrooms have immunomodulatory and anti-cancer effects. Our aim was to study the regulatory mechanisms of Caco-2 cell response to water soluble P. ostreatus polysaccharide extract up to 72 hours. Specific enzymatic activities were assessed by kinetic measurements. The reduced glutathione content and the lipid peroxidation level were also analyzed. Protein expression of several heat shock proteins, Bcl-2 and metalloproteinases 2 and 9 were revealed by Western blot. Gelatin zymography assay was used to evaluate the MMP-2 and MMP-9 activities. Until the third day of exposure the total SOD activity decreased continuously by 30%, whereas GST and GR ones diminished by 17% respectively 30.5% compared to control. No significant changes were observed in CAT and G6PDH specific activities as well as in GSH and MDA concentration. After the third day of exposure a significant up-regulation of Hsp60 and Hsp90 expression and a down-regulation of Hsp70 one were registered. Bcl-2 protein levels were down-regulated by 50% in the first day of treatment but increased after 3 days. MMP-2 and 9 secretion in the culture medium was significantly reduced suggesting a diminished ability of invasion of colon cancer cells. Our data revealed that in vitro treatment with P. ostreatus aqueous polysaccharide extract does not induce apoptosis in Caco-2 cell line but it could inhibit the invasion of colon cancer cells through the basement membrane.

scholarly journals Development of prognosis model for colon cancer based on autophagy-related genes

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Xu Wang ◽  
Yuanmin Xu ◽  
Ting Li ◽  
Bo Chen ◽  
Wenqi Yang
Keyword(s):  
Colon Cancer ◽  
Regression Analysis ◽  
High Risk ◽  
Cancer Patients ◽  
Risk Score ◽  
Cox Regression ◽  
Patient Survival ◽  
Expression Profiles ◽  
Cox Regression Analysis ◽  
Risk Patients

Abstract Background Autophagy is an orderly catabolic process for degrading and removing unnecessary or dysfunctional cellular components such as proteins and organelles. Although autophagy is known to play an important role in various types of cancer, the effects of autophagy-related genes (ARGs) on colon cancer have not been well studied. Methods Expression profiles from ARGs in 457 colon cancer patients were retrieved from the TCGA database (https://portal.gdc.cancer.gov). Differentially expressed ARGs and ARGs related to overall patient survival were identified. Cox proportional-hazard models were used to investigate the association between ARG expression profiles and patient prognosis. Results Twenty ARGs were significantly associated with the overall survival of colon cancer patients. Five of these ARGs had a mutation rate ≥ 3%. Patients were divided into high-risk and low-risk groups based on Cox regression analysis of 8 ARGs. Low-risk patients had a significantly longer survival time than high-risk patients (p < 0.001). Univariate and multivariate Cox regression analysis showed that the resulting risk score, which was associated with infiltration depth and metastasis, could be an independent predictor of patient survival. A nomogram was established to predict 1-, 3-, and 5-year survival of colon cancer patients based on 5 independent prognosis factors, including the risk score. The prognostic nomogram with online webserver was more effective and convenient to provide information for researchers and clinicians. Conclusion The 8 ARGs can be used to predict the prognosis of patients and provide information for their individualized treatment.

scholarly journals Tumour‐suppressive effect of oestrogen receptor β in colorectal cancer patients, colon cancer cells, and a zebrafish model

2020 ◽  
Vol 251 (3) ◽  
pp. 297-309
Author(s):  
Geriolda Topi ◽  
Shakti Ranjan Satapathy ◽  
Pujarini Dash ◽  
Syrina Fred Mehrabi ◽  
Roy Ehrnström ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Oestrogen Receptor ◽  
Suppressive Effect ◽  
Colon Cancer Cells ◽  
Zebrafish Model ◽  
Colorectal Cancer Patients

scholarly journals Metabolism-Based Molecular Sub-Phenotyping Predict Ketogenic Diet Responses in Colorectal Cancer

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 356-356
Author(s):  
Meng Tang ◽  
Qi Zhang ◽  
Kangping Zhang ◽  
Xi Zhang ◽  
Hanping Shi
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Ketogenic Diet ◽  
Theoretical Basis ◽  
Nutritional Stress ◽  
Metabolic Reprogramming ◽  
Metabolic Phenotype ◽  
Colon Cancer Cells ◽  
Metabolic Heterogeneity

Abstract Objectives Current studies have confirmed that the sensitivity of the ketogenic diet (KD) therapy for cancer depends on the low expression of ketolytic enzymes. However, increasing evidence showed that heterogeneity of tumor metabolism leads to inconsistent efficacies of KD therapy, which broke the illusion of the possibility of cancer treatment. Our study aims to construct colon cancer metabolism-related molecular subtyping. Furthermore, to explore the metabolic heterogeneity in diverse colon cancer cells and illuminate the mechanisms of mitochondrial metabolic reprogramming. Thus, providing a theoretical basis for clinical nutritional therapy and combined intervention measures based on metabolic molecular phenotyping. Methods We selected 19 genes associated with glucose and the keto-body metabolic pathway, then constructed a prognostic gene signature by LASSO and KM curve.  Based on the screened metabolic molecules, we further explored the nutrition metabolic heterogeneity and illuminate our understanding of mitochondrial metabolic reprogramming under nutritional stress in vivo. Results Through the integration of patients’ transcriptomics data,  we stratified colon cancer patients into three significant phenotypes with distinct glycolytic and ketolytic characteristics. We identified glycolysis + subtype with either GLUT1 or PFKFB3 overexpression, and ketolysis + subtype with either OXCT1 or ACAT1 deficiency.  In general, combining glycolysis+/ketolysis-phenotype demonstrated the worst prognosis. Furthermore, we discovered the metabolic heterogeneity through western blot and energy metabolic phenotype analysis which also confirmed that these different colon cancer cells showed great significance in metabolic reprogramming under nutritional stress. Conclusions The multi-target combination of metabolic phenotyping proved to be a foundation for individualized molecular stratified treatment which plays an essential role in predicting effectiveness of nutritional modulation therapy among colon cancer patients. It provided a theoretical basis for the clinical trial of KD therapy for patients with specific metabolic subtypes of colon cancer. Funding Sources The National Key Research and Development Program: The key technology of palliative care and nursing for cancer patients.

scholarly journals GLUT5 regulation by AKT1/3-miR-125b-5p downregulation induces migratory activity and drug resistance in TLR-modified colorectal cancer cells

2020 ◽  
Vol 41 (10) ◽  
pp. 1329-1340 ◽  
Author(s):  
Ga-Bin Park ◽  
Jee-Yeong Jeong ◽  
Daejin Kim
Keyword(s):  
Colon Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Cell Metabolism ◽  
Enzyme Activation ◽  
Migration And Invasion ◽  
Drug Resistant ◽  
Cancer Resistance ◽  
Colon Cancer Cells ◽  
Migratory Activity

Abstract In cancer, resistance to chemotherapy is one of the main reasons for therapeutic failure. Cells that survive after treatment with anticancer drugs undergo various changes, including in cell metabolism. In this study, we investigated the effects of AKT-mediated miR-125b-5p alteration on metabolic changes and examined how these molecules enhance migration and induce drug resistance in colon cancer cells. AKT1 and AKT3 activation in drug-resistant colon cancer cells caused aberrant downregulation of miR-125b-5p, leading to GLUT5 expression. Targeted inhibition of AKT1 and AKT3 restored miR-125b-5p expression and prevented glycolysis- and lipogenesis-related enzyme activation. In addition, restoring the level of miR-125b-5p by transfection with the mimic sequence not only significantly blocked the production of lactate and intracellular fatty acids but also suppressed the migration and invasion of chemoresistant colon cancer cells. GLUT5 silencing with small interfering RNA attenuated mesenchymal marker expression and migratory activity in drug-resistant colon cancer cells. Additionally, treatment with 2,5-anhydro-d-mannitol resensitized chemoresistant cancer cells to oxaliplatin and 5-fluorouracil. In conclusion, our findings suggest that changes in miR-125b-5p and GLUT5 expression after chemotherapy can serve as a new marker to indicate metabolic change-induced migration and drug resistance development.

scholarly journals A Tryptophan Metabolite, 8-Hydroxyquinaldic Acid, Exerts Antiproliferative and Anti-Migratory Effects on Colorectal Cancer Cells

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1655 ◽  
Author(s):  
Katarzyna Walczak ◽  
Ewa Langner ◽  
Karolina Szalast ◽  
Anna Makuch-Kocka ◽  
Piotr Pożarowski ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Mitochondrial Activity ◽  
Cell Cycle Regulators ◽  
Migratory Activity ◽  
Colorectal Cancer Cells ◽  
Induced Changes ◽  
Ht 29

8-Hydroxyquinaldic acid, the end-metabolite of tryptophan, is well-known metal chelator; however, its role in humans, especially in cancer promotion and progression, has not been fully revealed. Importantly, 8-hydroxyquinaldic acid is the analog of kynurenic acid with evidenced antiproliferative activity towards various cancer cells. In this study, we revealed that 8-hydroxyquinaldic acid inhibited not only proliferation and mitochondrial activity in colon cancer HT-29 and LS-180 cells, but it also decreased DNA synthesis up to 90.9% for HT-29 cells and 76.1% for LS-180 cells. 8-Hydroxyquinaldic acid induced changes in protein expression of cell cycle regulators (CDK4, CDK6, cyclin D1, cyclin E) and CDKs inhibitors (p21 Waf1/Cip1, p27 Kip1), but the effect was dependent on the tested cell line. Moreover, 8-hydroxyquinaldic acid inhibited migration of colon cancer HT-29 and LS-180 cells and increased the expression of β-catenin and E-cadherin. Importantly, antiproliferative and anti-migratory concentrations of 8-hydroxyquinaldic acid were non-toxic in vitro and in vivo. We reported for the first time antiproliferative and anti-migratory activity of 8-hydroxyquinaldic acid against colon cancer HT-29 and LS-180 cells.

Gene expression profiles of folate deficient colon cancer cells

2003 ◽  
Vol 124 (4) ◽  
pp. A239
Author(s):  
Petar Novakovic ◽  
Kyoung-Jin Sohn ◽  
Young-In J. Kim
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Colon Cancer Cells
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