scholarly journals The Sirtuin 3 Expression Profile Is Associated with Pathological and Clinical Outcomes in Colon Cancer Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Chunyuan Liu ◽  
Zonghai Huang ◽  
Hong Jiang ◽  
Fujun Shi
Keyword(s):  
Colon Cancer ◽  
Clinical Outcomes ◽  
Biological Behavior ◽  
Sirtuin 3 ◽  
Cancer Specific Survival ◽  
Colon Cells ◽  
Tumor Stages ◽  
Colon Cell ◽  
Sirt3 Expression

Aim.To investigate the correlation between Sirtuin 3 (SIRT3) expression and the clinical outcome of patients with colon cancer.Methods. The tumor specimens from 127 patients with colon cancer were obtained for SIRT3 immunohistochemical staining. Patients were followed up. Inin vitrostudy, SIRT3 gene was inhibited to observe the effects of SIRT3 on the biological behavior of cultured colon cells.Results. The SIRT3 expression level was found to be significantly associated with the lymph node metastasis (P<0.001) and tumor stages (P<0.001). The colon cancer-specific survival was 64.6% among patients with high SIRT3 expressions and 88.6% among patients with low SIRT3 expressions (log-rankP=0.016). The overall survival was 80.2% among patients with low SIRT3 expressions and 55.9% among patients with high SIRT3 expressions (log-rankP=0.002).In vitrostudy showed that silencing of SIRT3 gene inhibited the proliferation, invasion, and cells migration but increased the apoptosis in the cultured colon cell lines.Conclusion. This study provides evidence supporting that SIRT3 is closely associated with the clinical outcomes of colon cancer. SIRT3 may be considered as a marker for colon cancer.

scholarly journals Nigella Sativa’s Protection Against 7,12 Dimethylbenz [A] Anthracene -Induced Colon Carcinogenesis in Rats

Molekul ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. 262
Author(s):  
Heny Ekowati ◽  
Firster Nugroho ◽  
Iskandar Sobri
Keyword(s):  
Colon Cancer ◽  
Corn Oil ◽  
Nigella Sativa ◽  
Alternative Therapy ◽  
Rat Colon ◽  
Control Group ◽  
Colon Cells ◽  
Group I ◽  
Colon Cell

Colon cancer is the third most common cause of death from cancer worldwide. Recently, natural products have been widely used as an alternative therapy for colon cancer. Previous studies have reported that Nigella sativa has chemopreventive activity in vitro and in vivo.This study aimed to evaluate the effect of Nigella sativa seed (NSS) on rat-colon cell after initiation of 7,12-dimethylbenz [a] anthracene. Rats were divided into five groups, 12 rats in each group: Group I was given 7,12dimetilbenz [a] anthracene (DMBA) orally 20 mg/kgBW twice a week for five weeks, group V is the solvent control group was given corn oil. The other three groups were given DMBA + NSS, at the dosage of 250 mg/kgBW, 500 mg/kgBW and 750 mg/kgBW. NSS extract was dissolved in corn oil and administered daily per oral during the next two weeks before and during the initiation of DMBA. After 16 weeks, all rats were sacrificed. H&E staining showed that necrosis activity was lower in treated groups compared to DMBA group. AgNOR staining showed mAgNOR was significantly decrease following the increasing dose of NSS (250 mg/kgBW, 500 mg/kgBW and 750 mg/kgBW) were subsequently 1.62 ± 0.086, 1.60 ± 0.101 and 1.39 ± 0.049 (p<0.05). The results showed that NNS reduce the damage of colon cells and inhibit colon cell proliferation in DMBA induced rats.

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.

Effect of the ADAPT strategy on dormant CD133+ colon cancer stem cells (CSC) and molecular complete remission measured by peripheral blood mononuclear (PBMC) CD133 mRNA.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14153-e14153
Author(s):  
Edward H. Lin ◽  
Yu Xiazhen ◽  
Xi C He ◽  
Xifeng Wu ◽  
Yang Xie ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Median Survival ◽  
Treatment Protocol ◽  
Mrna Levels ◽  
Peripheral Blood Mononuclear ◽  
Colon Cells ◽  
Ca Ix ◽  
The Impact

e14153 Background: The median survival for patients with unresectable metastatic colorectal cancer (CRC) is ~2 years with modern chemotherapy which yields only 5-10% complete responses (CR) including metastasectomy. Recurrences after CR are very common thanks to presence of dormant CSC that are best targeted by our proposed two-step ADAPT strategy: activate from dormancy and potentiate targeting. We examine this strategy in various CRC models and reviewed the impact on stemess including CD133 mRNA, a circulating CSC marker that predict colon cancer relapse. Methods: Different CRC models (in vitro and in vivo) were interrogated similar to clinical ADAPT treatment protocol using capecitabine (or 5FU) plus celecoxib. We also conducted IRB approved retrospective review of unresectable metastatic CRC patients treated ADAPT therapy and in those who also had PBMC CD133 mRNA measured. Results: Contrary to 5FU, which eliminates proliferating CRC cells via apoptosis but also stimulates stemness, celecoxib preferentially deplete CD133+ colon cells and exert potent stemness inhibition via rapid tumor necrosis by perturbing hypoxia and energy metabolism via CA-IX. Following response to first-line chemotherapy, ADAPT strategy plus radiation improved CR or near CR rate to 49/126 (40%) in unresectable CRC patients whose median survival had reached 92.7 months (95% CI, 53.5 months - not reached). Paradoxically, none surgical CR patients (n= 16) enjoyed 100% 5-year relapse free survival compared to 42% of surgical patients (p = 0.04). The PBMC CD133 mRNA in five long-term CR patients were 0.0024, 0.29, 0.5, 0.56, 2.96 respectively, all below previously reported cutoff value of 4.79 for recurrence and far below CD133 mRNA levels (28, 375, 3997, 15662, 83240) in none CR patients. Conclusions: ADAPT plus radiation preferentially targets colon CSC via hypoxia/CA-IX and improves clinical CR rate and molecular CR as measured by PBMC CD133 mRNA. We are actively interrogating the effects of ADAPT strategies in a phase II study funded by Gateway in CRC patients and in genetic CRC animal models.

scholarly journals Antitumor Activity of Nitazoxanide against Colon Cancers: Molecular Docking and Experimental Studies Based on Wnt/β-Catenin Signaling Inhibition

2021 ◽  
Vol 22 (10) ◽  
pp. 5213
Author(s):  
Noha M. Abd El-Fadeal ◽  
Mohamed S. Nafie ◽  
Mohammed K. El-kherbetawy ◽  
Amr El-mistekawy ◽  
Hala M. F. Mohammad ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cytotoxic Effect ◽  
Glycogen Synthase ◽  
Experimental Studies ◽  
Nuclear Antigen ◽  
Normal Colon ◽  
Colon Cells ◽  
Hct 116 ◽  
Gsk 3Β

In colon cancer, wingless (Wnt)/β-catenin signaling is frequently upregulated; however, the creation of a molecular therapeutic agent targeting this pathway is still under investigation. This research aimed to study how nitazoxanide can affect Wnt/β-catenin signaling in colon cancer cells (HCT-116) and a mouse colon cancer model. Our study included 2 experiments; the first was to test the cytotoxic activity of nitazoxanide in an in vitro study on a colon cancer cell line (HCT-116) versus normal colon cells (FHC) and to highlight the proapoptotic effect by MTT assay, flow cytometry and real-time polymerase chain reaction (RT-PCR). The second experiment tested the in vivo cytotoxic effect of nitazoxanide against 1,2-dimethylhydrazine (DMH) prompted cancer in mice. Mice were grouped as saline, DMH control and DMH + nitazoxanide [100 or 200 mg per kg]. Colon levels of Wnt and β-catenin proteins were assessed by Western blotting while proliferation was measured via immunostaining for proliferating cell nuclear antigen (PCNA). Treating HCT-116 cells with nitazoxanide (inhibitory concentration 50 (IC50) = 11.07 µM) revealed that it has a more cytotoxic effect when compared to 5-flurouracil (IC50 = 11.36 µM). Moreover, it showed relatively high IC50 value (non-cytotoxic) against the normal colon cells. Nitazoxanide induced apoptosis by 15.86-fold compared to control and arrested the cell cycle. Furthermore, nitazoxanide upregulated proapoptotic proteins (P53 and BAX) and caspases but downregulated BCL-2. Nitazoxanide downregulated Wnt/β-catenin/glycogen synthase kinase-3β (GSK-3β) signaling and PCNA staining in the current mouse model. Hence, our findings highlighted the cytotoxic effect of nitazoxanide and pointed out the effect on Wnt/β-catenin/GSK-3β signaling.

scholarly journals Mevastatin in colon cancer by spectroscopic and microscopic methods - Raman imaging and AFM studies

2021 ◽  
Author(s):  
Karolina Beton ◽  
Piotr Wysocki ◽  
Beata Brozek-Pluska
Keyword(s):  
Colon Cancer ◽  
Medical Science ◽  
Mevalonic Acid ◽  
Biologically Active ◽  
In Vivo Studies ◽  
Normal Cells ◽  
Colon Cells ◽  
Cancerous Cells

One of the most important areas of medical science is oncology, which is responsible for both the diagnostics and treatment of cancer diseases. Simultaneously one of the main challenges of oncology is the development of modern drugs effective in the fight against cancer. Statins are a group of biologically active compounds with the activity of 3-hydroxy-3-methyl glutaryl-CoA reductase inhibitors, an enzyme catalyzing the reduction of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) to mevalonic acid. By acting on this enzyme, statins inhibit the endogenous cholesterol synthesis which in turn causes the reduction of its systemic concentrations. However, in vitro and in vivo studies confirm also the cytostatic and cytotoxic effects of statins against various types of cancer cells including colon cancer. In the presented studies the influence of mevastatin on cancerous colon cells CaCo-2 by Raman spectroscopy and imaging is discussed and compared with biochemistry characteristic for normal colon cells CCD-18Co. Based on vibrational features of colon cells: normal cells CCD-18Co, cancerous cells CaCo-2 and cancerous cells CaCo-2 treated by mevastatin in different concentrations and incubation times we have confirm the influence of this statin on biochemistry composition of cancerous human colon cells. Moreover, the spectroscopic results for colon normal cells and cancerous cells based on data typical for nucleic acids, proteins, lipids have been compared. The cytotoxisity of mevastatin was determined by using XTT tests.

scholarly journals Apelin gene therapy increases myocardial vascular density and ameliorates diabetic cardiomyopathy via upregulation of sirtuin 3

2014 ◽  
Vol 306 (4) ◽  
pp. H585-H597 ◽  
Author(s):  
Heng Zeng ◽  
Xiaochen He ◽  
Xuwei Hou ◽  
Lanfang Li ◽  
Jian-Xiong Chen
Keyword(s):  
Gene Therapy ◽  
Diabetic Cardiomyopathy ◽  
Vascular Density ◽  
Wild Type ◽  
Sirtuin 3 ◽  
Ros Formation ◽  
Sirt3 Expression ◽  
In Vitro Treatment ◽  
Angiopoietin 1

Microvascular insufficiency contributes to cardiac hypertrophy and worsens heart dysfunction in diabetic cardiomyopathy. Our recent study shows that apelin may protect ischemic heart failure via upregulation of sirtuin 3 (Sirt3) and angiogenesis. This study investigated whether apelin promotes angiogenesis and ameliorates diabetic cardiomyopathy via activation of Sirt3. Wild-type (WT) and diabetic db/db mice were administrated with adenovirus-apelin to overexpressing apelin. In WT mice, overexpression of apelin increased Sirt3, VEGF/VEGFR2, and angiopoietin-1 (Ang-1)/Tie-2 expression in the heart. In vitro, treatment of endothelial cells (EC) with apelin increased VEGF and Ang-1 expression. In EC isolated from Sirt3KO mice, however, apelin treatment did not upregulate VEGF and Ang-1 expression. Moreover, apelin-induced angiogenesis was diminished in Sirt3KO mice. In db/db mice, the basal levels of apelin and Sirt3 expression were significantly reduced in the heart. This was accompanied by a significant reduction of capillary and arteriole densities in the heart. Overexpression of apelin increased Sirt3, VEGF/VEGFR2, and Ang-1/Tie-2 expression together with improved vascular density in db/db mice. Overexpression of apelin further improved cardiac function in db/db mice. Treatment with apelin significantly attenuated high glucose (HG)-induced reactive oxygen species (ROS) formation and EC apoptosis. The protection of apelin against HG-induced ROS formation and EC apoptosis was diminished in Sirt3KO-EC. We conclude that apelin gene therapy increases vascular density and alleviates diabetic cardiomyopathy by a mechanism involving activation of Sirt3 and upregulation of VEGF/VEGFR2 and Ang-1/Tie-2 expression.

scholarly journals ORAI3 contributes to hypoxia-inducible factor 1/2α-sensitive colon cell migration

2021 ◽  
Author(s):  
D. Zhu ◽  
R. He ◽  
W. Yu ◽  
C. Li ◽  
H. Cheng ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Migration ◽  
Cancer Progression ◽  
Hypoxia Inducible Factor ◽  
Luciferase Assay ◽  
Hypoxia Inducible Factor 1 ◽  
Colon Cancer Progression ◽  
Colon Cell ◽  
Migration Capacity

AbstractBackgroundHypoxia is a pivotal initiator of tumor angiogenesis and growth through the stabilization of hypoxia-inducible factors (HIFs). This study set out to examine the involvement of HIF-1α and HIF-2α in colon cancer and ascertained whether ORAI3 was involved in the pathway.Materials and methodsPatients and murine models as well as human colorectal adenocarcinoma tumor (CW2) cells were included to examine the levels of ORAI1/3 and HIF-1/2α levels. Calcium imaging was utilized to ascertain the activity of calcium channel. Scratch assay was used to assess the migration capacity of the cells.ResultsTumors from murine colon cancer xenograft models and patients with colon cancer displayed high ORAI1/3 and HIF-1/2α levels. Hypoxia treatment, mimicking the tumor microenvironment in vitro, increased ORAI1/3 and HIF-1/2α expression as well as store-operated Ca2+ entry (SOCE). Of note is that HIF-1/2α silencing decreased SOCE, and HIF-1/2α overexpression facilitated SOCE. Furthermore, ORAI3 rather than ORAI1 expression was inhibited by HIF-1/2α silencing while increased by ML228. Luciferase assay also confirmed that ORAI3 was elevated in the presence of ML228, indicating the linkage between HIF-1/2α and ORAI3. Additionally, colony-forming potential and cell migration capacity were decreased in siHIF-1α and siHIF-2α as well as siORAI3 cells, and the facilitating effect of ML228 on cell migration and colony-forming potential was also decreased in siORAI3 CW-2 cells, which points out the importance of ORAI3 in HIF1/2α pathway.ConclusionOur findings allow to conclude that both HIF-1α and HIF-2α facilitate ORAI3 expression, hence enhancing colon cancer progression.

scholarly journals MicroRNA-let-7 Targets HMGA2 to Regulate the Proliferation, Migration, and Invasion of Colon Cancer Cell HCT116

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Zheng Chen ◽  
Jiheng Liu
Keyword(s):  
Colon Cancer ◽  
Cancer Cell ◽  
Colon Cancer Cell ◽  
Biological Behavior ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Luciferase Reporter Gene ◽  
New Gene ◽  
Hct116 Cells

Objective. To investigate the effect of microRNA-let-7 (miR-let-7) on the proliferation, migration, and invasion of colon cancer cell HCT116 in vitro and its regulatory mechanism on downstream HMGA2. Methods. It was planned to synthesize miR-let-7 overexpression (mimics) and interference expression (inhibitor) and transiently transfect colon cancer cell HCT116, detect the expression levels of miR-let-7 and HMGA2 in the cells after transfection and the targeted regulation effect of miR-let-7 on HMGA2, then detect the effect of upregulation/downregulation of miR-let-7 on HMGA2, and detect the proliferation, migration, and invasion of HCT116 cells. Results. The expression of miR-let-7 was downregulated, and the expression of HMGA2 was upregulated in HCT116. The expression of miR-let-7 increased significantly after HCT116 was transfected with miR-let-7 mimics. The expression of miR-let-7 decreased significantly after HCT116 was transfected with miR-let-7 inhibitor. The bioinformatics websites predicted that miR-let-7 has a binding site with HMGA2, and the dual-luciferase reporter gene experiment detected that miR-let-7 has a targeting relationship with HMGA2. The expression of HMGA2 decreased after HCT116 was transfected with miR-let-7 mimics; the expression of HMGA2 increased after HCT116 was transfected with miR-let-7 inhibitor. After upregulating miR-let-7, the proliferation, migration, and invasion ability of HCT116 was weakened. After miR-let-7 was inhibited, the proliferation, migration, and invasion ability of HCT116 was enhanced. Conclusion. Abnormal expression of miR-let-7 is an important factor affecting the proliferation, migration, and invasion of HCT116 cells, and it can promote or inhibit the biological behavior of cancer cells by targeting the expression of HMGA2. This study provides ideas for the drug development of new gene targets.

scholarly journals Mybl2, downregulated during colon epithelial cell maturation, is suppressed by miR-365

2011 ◽  
Vol 301 (3) ◽  
pp. G508-G518 ◽  
Author(s):  
Michael Papetti ◽  
Leonard H. Augenlicht
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Micro Rna ◽  
Cell Maturation ◽  
Cell Phenotype ◽  
Colon Cells ◽  
Colon Cell ◽  
Immortalized Cell

Altered profiles of gene expression reflect the reprogramming of intestinal epithelial cells during their maturation along the crypt-luminal axis. To focus on genes important in this process, and how they in turn are regulated, we identified 14 transcripts commonly downregulated in expression during lineage-specific maturation of the immortalized cell lines Caco-2 (absorptive), HT29Cl16E (goblet), and HT29Cl19A (secretory) induced by contact inhibition of growth or the short-chain fatty acid butyrate. One such gene, Mybl2 (Myb-related protein B), has been linked to the stem cell phenotype, and we report is also markedly suppressed in maturing cells along the crypt-luminal axis in vivo. Mybl2 is not significantly downregulated transcriptionally during colon cell maturation, but we identified a potential micro-RNA (miRNA)-binding sequence in the Mybl2 3′-untranslated region that mediates reporter gene suppression in differentiating colon cells. Accordingly, miRNAs predicted to bind this functional target are upregulated in differentiating colon epithelial cells in vitro and in vivo; expression of one of these, hsa-miR-365 (but not hsa-324–5p), suppresses Mybl2 protein expression in proliferating Caco-2 cells. These data demonstrate that miRNA silencing plays an important role in regulating gene expression in maturing colon epithelial cells, and that utilizing a target-centered approach, rather than profiling global miRNA expression, can identify physiologically relevant, functional miRNAs.

scholarly journals Histone lysine-specific demethylase 1 induced renal fibrosis via decreasing sirtuin 3 expression and activating TGF-β1/Smad3 pathway in diabetic nephropathy

2022 ◽  
Vol 14 (1) ◽  
Author(s):  
Lina Dong ◽  
Lei Yu ◽  
Jin Zhong
Keyword(s):  
Diabetic Nephropathy ◽  
Renal Injury ◽  
Renal Fibrosis ◽  
Sirtuin 3 ◽  
Histone Lysine ◽  
Lysine Specific Demethylase ◽  
Sirt3 Expression ◽  
Tgf Β1

Abstract Objective Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Histone lysine-specific demethylase 1 (LSD1) is a flavin-containing amino oxidase that can repress or activate transcription. The aim of this study is to explore the mechanism of LSD1 aggravating DN-induced renal fibrosis. Methods The STZ-induced DN rat model was established for in vivo study. The rats were divided into four groups: Sham, STZ, STZ + Ad-shNC and Ad-shLSD1. The Hematoxylin–eosin (HE) staining was used to evaluate the renal injury. The Immunofluorescence assay was used to determine the LSD1, Fibronectin and α-SMA expression. The related protein expression was detected by western blot. Results Knockdown of LSD1 alleviated STZ-induced renal injury. Moreover, knockdown of LSD1 decreased the expression of serum biochemical markers, containing urine output (24 h), urinary protein (24 h), serum creatinine, BUN and UACR. Furthermore, we proved that knockdown of LSD1 alleviated renal fibrosis in STZ-induced DN rats. In vitro, knockdown of LSD1 suppressed NRK-49F cells activation and overexpression of LSD1 induced renal fibrosis. In addition, knockdown of LSD1 could deactivate TGF-β1/Smad3 pathway and promote sirtuin 3 (SIRT3) expression in vivo and in vitro. The rescue experiments confirmed that LSD1 induced renal fibrosis via decreasing SIRT3 expression and activating TGF-β1/Smad3 pathway. Conclusion LSD1 deficiency leads to alleviate STZ-induced renal injury and overexpression of LSD1 induces renal fibrosis via decreasing SIRT3 expression and activating TGF-β1/Smad3 pathway, which provides a reasonable strategy for developing novel drugs targeting LDS1 to block renal fibrosis.

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