scholarly journals Tumidulin, a Lichen Secondary Metabolite, Decreases the Stemness Potential of Colorectal Cancer Cells

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2968 ◽  
Author(s):  
Yi Yang ◽  
Suresh Bhosle ◽  
Young Yu ◽  
So-Yeon Park ◽  
Rui Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Zinc Finger Protein ◽  
Protein Levels ◽  
Ht29 Cells ◽  
Colorectal Cancer Cells ◽  
Reporter Assays ◽  
Cluster Of Differentiation ◽  
Acetone Extracts ◽  
First Time

Lichens produce various unique chemicals that are used in the pharmaceutical industry. To screen for novel lichen secondary metabolites that inhibit the stemness potential of colorectal cancer cells, we tested acetone extracts of 11 lichen samples collected in Chile. Tumidulin, isolated from Niebla sp., reduced spheroid formation in CSC221, DLD1, and HT29 cells. In addition, mRNA expressions and protein levels of cancer stem markers aldehyde dehydrogenase-1 (ALDH1), cluster of differentiation 133 (CD133), CD44, Lgr5, and Musashi-1 were reduced after tumidulin treatment. Tumidulin decreased the transcriptional activity of the glioma-associated oncogene homolog zinc finger protein (Gli) promoter in reporter assays, and western blotting confirmed decreased Gli1, Gli2, and Smoothened (SMO) protein levels. Moreover, the tumidulin activity was not observed in the presence of Gli and SMO inhibitors. Together, these results demonstrate for the first time that tumidulin is a potent inhibitor of colorectal cancer cell stemness.

scholarly journals miR193a-5p Mediated ZNF746 and c-Myc Signaling Axis Is Critically Involved in Morusin Induced Apoptosis in Colorectal Cancer Cells

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2065
Author(s):  
Woon-Yi Park ◽  
Hyo-Jung Lee ◽  
Deok-Yong Sim ◽  
Eunji Im ◽  
Ji-Eon Park ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Zinc Finger Protein ◽  
Target Therapy ◽  
Colorectal Cancer Cells ◽  
Signaling Axis ◽  
Novel Target ◽  
The Stability ◽  
Induced Apoptosis ◽  
Hct116 Cells

Novel target therapy is on the spotlight for effective cancer therapy. Hence, in the present study, the underlying apoptotic mechanism of Morusin was explored in association with miR193a-5p mediated ZNF746/c-Myc signaling axis in colorectal cancer cells (CRCs). Herein, Morusin reduced the viability and the number of colonies in HCT116 and SW480 CRCs. Additionally, Morusin increased sub-G1 population, cleavages of poly (ADP-ribose) polymerase (PARP) and caspase-3 and inhibited the expression of zinc finger protein 746 (ZNF746) and c-Myc in HCT116 and SW480 cells. Conversely, overexpression of ZNF746 suppressed the ability of Morusin to abrogate the expression of c-Myc in HCT116 cells, as ZNF746 enhanced the stability of c-Myc via their direct binding through nuclear colocalization in HCT116 cells by immunofluorescence and immunoprecipitation. Notably, Morusin upregulated miR193a-5p as a tumor suppressor, while miR193a-5p inhibitor masked the ability of Morusin to reduce the expression of ZNF746, c-Myc, and pro-PARP in HCT116 cells. To our knowledge, these findings provide the novel insight on miR193a-5p mediated inhibition of ZNF746/c-Myc signaling in Morusin induced apoptosis in CRCs.

scholarly journals Quercetin inhibits the tumorigenesis of colorectal cancer cells through downregulation of hsa_circ_0006990

2021 ◽  
Author(s):  
Bin Chen ◽  
Haijuan Xiao ◽  
Linguangjin Wu ◽  
Ting Wang ◽  
Shuyun Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Colony Formation Assay ◽  
Transwell Assay ◽  
Protein Levels ◽  
Colorectal Cancer Cells ◽  
New Strategies ◽  
Malignant Behavior

Abstract Background This study was intended to investigate the function of Quercetin in chemoresistant colorectal cancer (CRC) cells. In addition, this research aimed to explore the mechanism by which Quercetin regulates the malignant behavior of CRC cells. Methods To induce THP-1 cells into M2 tumor-associated macrophages (M2-TAMs), THP-1 cells were stimulated by PMA and IL-4. MDC staining was used to investigate the autophagy in M2-TAMs. Meanwhile, cell proliferation was tested by colony formation assay. In addition, wound healing and transwell assay were performed to detect the cell migration and invasion, respectively. Dual luciferase assay was used to investigate the correlation between hsa_circ_0006990 and miR-132-3p/miR-532-3p. Furthermore, mRNA and protein levels were detected by RT-qPCR and western blot, respectively. Results Quercetin suppressed autophagy of M2-TAMs. In addition, M2-TAMs significantly inhibited the apoptosis and promoted the proliferation of CRC cells, while this phenomenon was reversed by Quercetin. Meanwhile, the expression of hsa_circ_0006990 in CRC cells was decreased by M2-TAMs, while Quercetin reversed this phenomenon. Furthermore, overexpression of hsa_circ_0006990 significantly reversed the anti-tumor effect of Quercetin on CRC. Conclusion Quercetin inhibited the tumorigenesis of colorectal cancer cells through downregulation of hsa_circ_0006990. Thus, our study might shed new lights on exploring the new strategies against CRC.

Verbascoside Attenuates Rac-1 and HIF-1α Signaling Cascade in Colorectal Cancer Cells

2019 ◽  
Vol 18 (15) ◽  
pp. 2149-2155
Author(s):  
Danial Seyfi ◽  
Seyed B. Behzad ◽  
Mohammad Nabiuni ◽  
Kazem Parivar ◽  
Mohammad Tahmaseb ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Real Time ◽  
Real Time Pcr ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Ht29 Cells ◽  
Colorectal Cancer Cells

Objective: Metastasis phenotype is considered as the main challenge in colon cancer therapeutic methods. Furthermore, the side effects of conventional colorectal cancer treatment methods have attracted a lot of attention into natural ingredients. The aim of the study was to assess the molecular mechanism of verbascoside as natural bio-compound in human HT29 colon cancer cells. Methods: HT29 cells were cultured in RPMI-1640 medium containing 10% FBS and 1% penicillin/ streptomycin at 37°C and 5% CO2. HT-29 cells were treated with different concentrations of verbascoside (10, 20, 30, 40, 50, 70, 100 µg/ml) for 24 hours, then MTT assay was used to calculate 50% inhibitory concentration. The migration of the colon cancer cells was evaluated by scratch assay. To evaluate involved antiproliferative mechanism, Rac-1 (Ras-related C3 botulinum toxin substrate 1) and HIF-1α (hypoxia-inducible factor-1α) related gene expression were evaluated by Real Time PCR. Results: The results showed that verbascoside inhibited HT29 colon cancer cell proliferation dose-dependently and IC50 was evaluated as 50 μg/ml (***P<0.001). The results of wound healing assay demonstrated verbascoside decreased cell migration in a dose dependent manner. In the IC50 treated HT29 cells metastatic progression was significantly suppressed as **P<0.01. The results of Real Time PCR showed an attenuating effect of verbascoside on Rac-1, Zeb-1 (zinc finger E-box binding homeobox 1), Arp2 (Actin-Related Proteins), Pak1 (p21 (RAC1) activated kinase 1), VEGF (Vascular endothelial growth factor) and HIF-1α as Epithelial-Mesenchymal Transition markers. The down regulation of mRNA levels was Rac-1= 15.38, HIF-1 α = 16.66, Pak-1, Arp-2= 6.25, VEGF=24.39, Zeb-1=35.71 in HT29 cells treated with IC50 concentration of verbascoside. Conclusion: Colorectal cancer cells induce Rac-1 and HIF-1α overexpression which plays an important role in the activation and progression of cell motility, angiogenesis and metastasis. Overall results showed that verbascoside elucidated significant anti-metastatic and anti-invasion activities through suppression of Rac-1, HIF-1α, and Zeb-1 signaling pathway and it may be a suitable candidate to overwhelm colon cancer metastatic phenotype.

scholarly journals Arginine Deiminase Induces Immunogenic Cell Death and Is Enhanced by N-acetylcysteine in Murine MC38 Colorectal Cancer Cells and MDA-MB-231 Human Breast Cancer Cells In Vitro

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 511
Author(s):  
Zhiying Huang ◽  
Haifeng Hu
Keyword(s):  
Colorectal Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
High Mobility ◽  
Arginine Deiminase ◽  
Immunogenic Cell Death ◽  
Anticancer Properties ◽  
Colorectal Cancer Cells ◽  
First Time

The use of arginine deiminase (ADI) for arginine depletion therapy is an attractive anticancer approach. Combination strategies are needed to overcome the resistance of severe types of cancer cells to this monotherapy. In the current study, we report, for the first time, that the antioxidant N-acetylcysteine (NAC), which has been used in therapeutic practices for several decades, is a potent enhancer for targeted therapy that utilizes arginine deiminase. We demonstrated that pegylated arginine deiminase (ADI-PEG 20) induces apoptosis and G0/G1 phase arrest in murine MC38 colorectal cancer cells; ADI-PEG 20 induces Ca2+ overload and decreases the mitochondrial membrane potential in MC38 cells. ADI-PEG 20 induced the most important immunogenic cell death (ICD)-associated feature: cell surface exposure of calreticulin (CRT). The antioxidant NAC enhanced the antitumor activity of ADI-PEG 20 and strengthened its ICD-associated features including the secretion of high mobility group box 1 (HMGB1) and adenosine triphosphate (ATP). In addition, these regimens resulted in phagocytosis of treated MC38 cancer cells by bone marrow-derived dendritic cells (BMDCs). In conclusion, we describe, for the first time, that NAC in combination with ADI-PEG 20 not only possesses unique cytotoxic anticancer properties but also triggers the hallmarks of immunogenic cell death. Hence, ADI-PEG 20 in combination with NAC may represent a promising approach to treat ADI-sensitive tumors while preventing relapse and metastasis.

scholarly journals Propofol Disrupts Aerobic Glycolysis in Colorectal Cancer Cells via Inactivation of the NMDAR-CAMKII-ERK Pathway

2018 ◽  
Vol 46 (2) ◽  
pp. 492-504 ◽  
Author(s):  
Xiangyuan Chen ◽  
Qichao Wu ◽  
Pengfei Sun ◽  
Yanjun Zhao ◽  
Minmin Zhu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Glucose Metabolism ◽  
Cancer Cells ◽  
Aerobic Glycolysis ◽  
Hypoxia Inducible Factor ◽  
Xenograft Model ◽  
Erk Pathway ◽  
Protein Levels ◽  
Colorectal Cancer Cells

Background/Aims: To investigate the effect of propofol on glucose metabolism in colorectal cancer cells and in an in vivo xenograft model. Methods: Glucose metabolism was assessed by measuring the extracellular acidification rate in HT29 and SW480 colorectal cancer cells. Quantitative real-time PCR and western blot analyses were used to detect mRNA and protein levels, respectively. Intracellular calcium was assessed by using a Fluo-3 AM fluorescence kit. Micro-positron emission tomography/computed tomography (microPET/CT) imaging was used to analyze glucose metabolism in the tumors of the xenograft model. Results: Propofol exposure induced a dose-dependent decrease of aerobic glycolysis in HT29 and SW480 colorectal cancer cells. MicroPET/CT indicated that propofol also inhibited 18F-FDG uptake in the xenograft model. In addition, hypoxia-inducible factor 1α (HIF1α) was also reduced by propofol dose-dependently. Propofol repressed the NMDAR-CAMKII-ERK pathway to inactivate HIF1α and therefore reduced glycolysis. Conclusion: Propofol inhibited aerobic glycolysis in colorectal cancer cells through the inactivation of the NMDAR-CAMKII-ERK pathway, which may facilitate a better understanding of the use of propofol in the clinical setting.

scholarly journals Cytotoxic Activity and Cell Cycle Analysis of Hexahydrocurcumin on SW 480 Human Colorectal Cancer Cells

2011 ◽  
Vol 6 (11) ◽  
pp. 1934578X1100601
Author(s):  
Chung-Yi Chen ◽  
Woei-Ling Yang ◽  
Soong-Yu Kuo
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Zingiber Officinale ◽  
Human Colorectal Cancer ◽  
Colorectal Cancer Cells ◽  
G0 Phase ◽  
First Time ◽  
Massive Accumulation ◽  
Human Colorectal Cancer Cells

The cytotoxicity of hexahydrocurcumin and its effect on the cell cycle in human colorectal cancer cells SW480 has been studied for the first time. The compound, extracted from Zingiber officinale, was shown to be cytotoxic to colorectal cancer cells. Treatment of SW480 cells with hexahydrocurcumin (100 μM) resulted in a massive accumulation of the cells in the G1/G0 phase of the cell cycle. The cytotoxic effect of hexahydrocurcumin may prove useful in cancer prevention.

scholarly journals Identification of zinc finger protein of the cerebellum 5 as a survival factor of prostate and colorectal cancer cells

2017 ◽  
Vol 108 (12) ◽  
pp. 2405-2412 ◽  
Author(s):  
Reiko Satow ◽  
Shota Inagaki ◽  
Chiaki Kato ◽  
Makoto Shimozawa ◽  
Kiyoko Fukami
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Survival Factor ◽  
Finger Protein ◽  
Colorectal Cancer Cells

scholarly journals NEDD9 Inhibition by miR-25-5p Activation Is Critically Involved in Co-Treatment of Melatonin- and Pterostilbene-Induced Apoptosis in Colorectal Cancer Cells

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1684 ◽  
Author(s):  
Ji Hoon Jung ◽  
Eun Ah Shin ◽  
Ju-Ha Kim ◽  
Deok Yong Sim ◽  
Hyemin Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Mrna Level ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Ki67 Expression ◽  
Ht29 Cells ◽  
Synergistic Cytotoxicity ◽  
Colorectal Cancer Cells ◽  
Induced Apoptosis ◽  
Apoptotic Mechanism

The underlying interaction between melatonin (MLT) and daily fruit intake still remains unclear to date, despite multibiological effects of MLT. Herein, the apoptotic mechanism by co-treatment of MLT and pterostilbene (Ptero) contained mainly in grape and blueberries was elucidated in colorectal cancers (CRCs). MLT and Ptero co-treatment (MLT+Ptero) showed synergistic cytotoxicity compared with MLT or Ptero alone, reduced the number of colonies and Ki67 expression, and also increased terminal deoxynucleotidyl transferase dUTP nick end labeling- (TUNEL) positive cells and reactive oxygen species (ROS) production in CRCs. Consistently, MLT+Ptero cleaved caspase 3 and poly (ADP-ribose) polymerase (PARP), activated sex-determining region Y-Box10 (SOX10), and also attenuated the expression of Bcl-xL, neural precursor cell expressed developmentally downregulated protein 9 (NEDD9), and SOX9 in CRCs. Additionally, MLT+Ptero induced differentially expressed microRNAs (upregulation: miR-25-5p, miR-542-5p, miR-711, miR-4725-3p, and miR-4484; downregulation: miR-4504, miR-668-3p, miR-3121-5p, miR-195-3p, and miR-5194) in HT29 cells. Consistently, MLT +Ptero upregulated miR-25-5p at mRNA level and conversely NEDD9 overexpression or miR-25-5p inhibitor reversed the ability of MLT+Ptero to increase cytotoxicity, suppress colony formation, and cleave PARP in CRCs. Furthermore, immunofluorescence confirmed miR-25-5p inhibitor reversed the reduced fluorescence of NEDD9 and increased SOX10 by MLT+Ptero in HT29 cells. Taken together, our findings provided evidence that MLT+Ptero enhances apoptosis via miR-25-5p mediated NEDD9 inhibition in colon cancer cells as a potent strategy for colorectal cancer therapy.

scholarly journals SKP1 promotes YAP-mediated colorectal cancer stemness via suppressing RASSF1

2020 ◽  
Author(s):  
Cong Tian ◽  
Tingyuan Lang ◽  
Jiangfeng Qiu ◽  
Kun Han ◽  
Lei Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Drug Target ◽  
Self Renewal ◽  
Protein Levels ◽  
Colorectal Cancer Cells ◽  
Underlying Mechanisms ◽  
And Migration

Abstract Background: Cancer stem cells (CSCs) have been recognized as an important drug target, however, the underlying mechanisms have not been fully understood. SKP1 is a traditional drug target for cancer therapy, while, whether SKP1 promotes colorectal cancer (CRC) stem cells (CRC-SCs) and the underlying mechanisms have remained elusive.Methods: Human CRC cell lines HCT-116 and HT-29 and primary human colorectal cancer cells were used in this study. Gene manipulation was performed by lentivirus system. The mRNA and protein levels were examined by qRT-PCR and western blot, respectively. Sphere formation and transwell assay were employed for examination of sphere-forming and migration capacities. The self-renewal capacity was determined by limiting dilution assay. The tumorigenicity was examined by xenograft model. The transcriptional activities of the promoters were examined by luciferase reporter assay. Co-immunoprecipitation assay was used to test protein-protein interaction. The transcription and protein-DNA interaction were examined by nuclear run-on and ChIP-PCR assay. The relationship between gene expression and survival was analyzed by Kaplan-meier analysis. The correlation between two genes was analyzed by Spearman analysis. Data are represented as mean ± s.d. and the significance was determined by Student’s t-test.Results: SKP1 is upregulated in colorectal cancer stem cells and predicts poor prognosis of colon cancer patients. Overexpression of SKP1 promotes the sphere-forming and migration capacities as well as self-renewal of CRC cells, and upregulates the expression of CSCs markers. In contrast, SKP1 depletion produces the opposite effects. SKP1 strengthens YAP activity and knockdown of YAP abolished the effect of SKP1 on the stemness of colorectal cancer cells. SKP1 suppresses RASSF1 at both mRNA and protein levels and overexpression of RASSF1 abolished the effect of SKP1.Conclusion: Our results demonstrated that SKP1 suppresses RASSF1 at both mRNA and protein level, attenuates Hippo signaling, activates YAP, and thereby promoting the stemness of CRC cells. Our works thus revealed a novel underlying mechanism of CRC-SCs maintenance and suggested a novel drug target for eradicating CRC-SCs.

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