scholarly journals Novel Xanthone Derivatives Impair Growth and Invasiveness of Colon Cancer Cells In Vitro

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1480
Author(s):  
Jakub Rech ◽  
Daniel Sypniewski ◽  
Dorota Żelaszczyk ◽  
Natalia Szkaradek ◽  
Wojciech Rogóż ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Gambogic Acid ◽  
Colon Cancer Cells ◽  
Xanthone Derivatives

Natural xanthones are a large group of compounds from which promising anticancer properties could be further developed by chemical modifications. This study aimed to investigate the influence of four novel xanthone derivatives based on a naturally occurring xanthone skeleton on the invasiveness of colon cancer cells in vitro. First, the concentrations required to inhibit growth of three colorectal cancer cell lines to 50% (GI50) of all the studied compounds, as well as the natural xanthones used as a reference (gambogic acid and α-mangostin), have been established (MTS reduction test). Next, the assays determining several aspects of the GI25 xanthones influence on colorectal cancer cells, including cytotoxicity, migration and invasion potential, interaction with extracellular matrix and endothelial cells, as well as expression of selected invasiveness related genes have been performed. Our results demonstrate that these novel xanthone derivatives impair colorectal cancer proliferation, motility, adhesion to extracellular matrix and to endothelial cells, and also induce apoptosis and cell death. Moreover, their activity is comparable to cisplatin and 5-fluorouracil, used as reference compounds. Conducted research indicates our compounds for further research and development as novel drugs in colorectal cancer treatment.

scholarly journals Atypical role of sprouty in colorectal cancer: sprouty repression inhibits epithelial–mesenchymal transition

Oncogene ◽  
2015 ◽  
Vol 35 (24) ◽  
pp. 3151-3162 ◽  
Author(s):  
Q Zhang ◽  
T Wei ◽  
K Shim ◽  
K Wright ◽  
K Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Colon Cancer Cells ◽  
Mesenchymal Transition ◽  
E Cadherin

Abstract Sprouty (SPRY) appears to act as a tumor suppressor in cancer, whereas we demonstrated that SPRY2 functions as a putative oncogene in colorectal cancer (CRC) (Oncogene, 2010, 29: 5241–5253). We investigated the mechanisms by which SPRY regulates epithelial–mesenchymal transition (EMT) in CRC. SPRY1 and SPRY2 mRNA transcripts were significantly upregulated in human CRC. Suppression of SPRY2 repressed AKT2 and EMT-inducing transcription factors and significantly increased E-cadherin expression. Concurrent downregulation of SPRY1 and SPRY2 also increased E-cadherin and suppressed mesenchymal markers in colon cancer cells. An inverse expression pattern between AKT2 and E-cadherin was established in a human CRC tissue microarray. SPRY2 negatively regulated miR-194-5p that interacts with AKT2 3′ untranslated region. Mir-194 mimics increased E-cadherin expression and suppressed cancer cell migration and invasion. By confocal microscopy, we demonstrated redistribution of E-cadherin to plasma membrane in colon cancer cells transfected with miR-194. Spry1 −/− and Spry2 −/− double mutant mouse embryonic fibroblasts exhibited decreased cell migration while acquiring several epithelial markers. In CRC, SPRY drive EMT and may serve as a biomarker of poor prognosis.

Validation of TPX2 as a novel prognostic marker for malignant progression and metastasis of colon cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 442-442 ◽  
Author(s):  
Ping Wei ◽  
Dawei Li ◽  
Ye Xu ◽  
Sanjun Cai
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Human Colon ◽  
Clinical Staging ◽  
Migration And Invasion ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
A Genome

442 Background: We previously identified aberrant overexpression of TPX2 in colon cancer by using a genome-wide gene expression profiling analysis. Here, we aimed to investigate its expression pattern, clinical significance, and biological function in colon cancer. Methods: The expression of TPX2 was analyzed in human colon cancer cell lines and tumor samples. The effect of TPX2 on cell proliferation, tumorigenesis and metastasis was examined in vitro and in vivo. Results: Overexpression of TPX2 was found in metastatic lesion of colon cancer, significantly higher than primary cancererous tissue and normal colon mucosa. Overexpression of TPX2 was significantly associated with the clinical staging, vessel invasion and metastasis. In survival analyses, patients with TPX2 expression had worse overall survival and metastasis free survival, suggesting that deregulation of TPX2 may contribute to the metastasis of colon cancer. Consistently, Silencing TPX2 inhibited proliferation and tumorigenicity of colon cancer cells both in vitro and in vivo. Strikingly, we found that TPX2 knockdown significantly attenuated the migration and invasion ability of colon cancer cells, which was further shown to be mechanistically associated with AKT mediated MMP9 activity. Conclusions: These findings suggest that TPX2 plays an important role in promoting tumorigenesis and metastasis of human colon cancer and may represent a novel prognostic biomarker and therapeutic target for the disease.

scholarly journals IRF4 overexpression promotes the transdifferentiation of tregs into macrophage‐like cells to inhibit the development of colon cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiwei Wang ◽  
Song Li ◽  
Honglang Li ◽  
Xiaoshuang Zhou ◽  
Huabin Wen ◽  
...  
Keyword(s):  
Colon Cancer ◽  
T Cells ◽  
Regulatory T Cells ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Colon Cancer Cells ◽  
Bcl6 Expression ◽  
Cancer Tissues

Abstract Background Interferon regulatory factor 4 (IRF4) is a transcription factor from the IRF factor family that exerts regulatory functions in the immune system and oncogenesis. However, the biological role of IRF4 in colon cancer is still unclear. The aim of this study is to investigate whether IRF4 participates in the immune response in colon cancer. Methods We compared the expression of IRF4, the number of regulatory T cells (Tregs) and macrophages in the colon cancer tissues and paracancerous colon tissues from colon cancer patients. Colon cancer mouse model was established by inoculation with colon cancer cells (SW480) as a xenograft tumor, and we observed tumor growth of colon cancer. Furthermore, the mechanism of action of IRF4 in transdifferentiation of Tregs into macrophage-like cells and the effect of IRF4 on colon cancer cells were investigated in vitro. Results IRF4 was severely down-regulated in the colon cancer tissues. Colon cancer tissues exhibited an increase in the number of regulatory T cells (Tregs) and macrophages. Furthermore, IRF4 overexpression repressed proliferation, migration and invasion of colon cancer cells (SW480 and HT116 cells). Moreover, IRF4 up-regulation ameliorated tumor growth of colon cancer by promoting the transdifferentiation of Tregs into macrophage-like cells through inhibition of BCL6 expression. Exosomes derived from colon cancer cells repressed IRF4 expression in Tregs by transmitting miR-27a-3p, miR-30a-5p and miR-320c. Conclusions IRF4 overexpression promoted the transdifferentiation of Tregs into macrophage-like cells to inhibit the occurrence and development of colon cancer. Thus, IRF4 may be a potential target for colon cancer treatment.

scholarly journals Identification of histone methyltransferase NSD2 as an important oncogenic gene in colorectal cancer

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Li-hao Zhao ◽  
Quan Li ◽  
Zhi-Jun Huang ◽  
Mi-Xue Sun ◽  
Jing-jing Lu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Histone Methyltransferase ◽  
Migration And Invasion ◽  
Colon Cancer Cells ◽  
Akt Activation ◽  
Primary Colon Cancer ◽  
Primary Colon

AbstractColorectal cancer (CRC) is the second common cause of cancer-related human mortalities. Dysregulation of histone 3 (H3) methylation could lead to transcriptional activation of multiple oncogenes, which is closely associated with CRC tumorigenesis and progression. Nuclear receptor-binding SET Domain protein 2 (NSD2) is a key histone methyltransferase catalyzing histone H3 lysine 36 dimethylation (H3K36me2). Its expression, the potential functions, and molecular mechanisms in CRC are studied here. Gene Expression Profiling Interactive Analysis (GEPIA) bioinformatics results showed that the NSD2 mRNA expression is elevated in both colon cancers and rectal cancers. Furthermore, NSD2 mRNA and protein expression levels in local colon cancer tissues are significantly higher than those in matched surrounding normal tissues. In primary human colon cancer cells and established CRC cell lines, shRNA-induced silencing or CRISPR/Cas9-induced knockout of NSD2 inhibited cell viability, proliferation, cell cycle progression, migration, and invasion. Furthermore, NSD2 shRNA or knockout induced mitochondrial depolarization, DNA damage, and apoptosis in the primary and established CRC cells. Contrarily, ectopic NSD2 overexpression in primary colon cancer cells further enhanced cell proliferation, migration, and invasion. H3K36me2, expressions of multiple oncogenes (ADAM9, EGFR, Sox2, Bcl-2, SYK, and MET) and Akt activation were significantly decreased after NSD2 silencing or knockout in primary colon cancer cells. Their levels were however increased after ectopic NSD2 overexpression. A catalytic inactive NSD2 (Y1179A) also inhibited H3K36me2, multiple oncogenes expression, and Akt activation, as well as cell proliferation and migration in primary colon cancer cells. In vivo, intratumoral injection of adeno-associated virus (AAV)-packed NSD2 shRNA largely inhibited primary colon cancer cell xenograft growth in nude mice. Together, NSD2 exerted oncogenic functions in CRC and could be a promising therapeutic target.

scholarly journals ID: 1029 Effects of carnosine on regulation of migration and invasion in human colorectal cancer cells

2017 ◽  
Vol 4 (S) ◽  
pp. 104 ◽  
Author(s):  
Po-Yu Lai ◽  
Shu-Chen Hsieh ◽  
Chih-Chung Wu ◽  
Shu-Ling Hsieh
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Human Colon ◽  
Migration And Invasion ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Hct 116 ◽  
Hct 116 Cells ◽  
Human Colon Cancer Cells

Colorectal cancer is the third most commonly diagnosed cancer in the word. Carnosine is an endogenous dipeptide found in vertebrate skeletal muscles. It is known to have anti-fatigue, antioxidative, antihypertensive, antidiabetic, and cancer inhibiting effects. However, little research has been done regarding its influence on the metastasis of colon cancer. This study cultivated HCT-116 human colon cancer cells as a test model in order to investigate the impact of carnosine on the migration and invasion of human colon cancer cells. The results showed that 48-hour treatments of HCT-116 cells with 0.5, 1, or 5 mM carnosine each significantly inhibited the migration ability of the cells (P < 0.05). The 48-hour treatments with 0.5, 1, or 5 mM carnosine were also found to significantly reduce MMP-9 activity (P < 0.05), but not MMP-2 expression. Furthermore, when HCT-116 cells treated with 1 or 5 mM carnosine, invasion ability are significantly decreased and significantly increased E-cadherin expression (P < 0.05). On the other hand, the protein of TIMP-1, an inhibitor of MMP-9, is signification increased after 1 or 5 mM carnosine treatment (P<0.05). In addition, the u-PA protein level are significantly decreased after carnosine treatment. The results indicate that carnosine can regulate the migration and invasion by regulating MMPs and its regulator molecular expression in HCT-116 cells.

scholarly journals Modifying Effects of Glucose and Insulin/Insulin-Like Growth Factors on Colon Cancer Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Şeyda Berk ◽  
Joseph A. M. J. L. Janssen ◽  
Peter M. van Koetsveld ◽  
Fadime Dogan ◽  
Naci Değerli ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Growth Factors ◽  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Experimental Studies ◽  
Colon Cancer Cells ◽  
Colorectal Cancer Cells ◽  
Insulin Like Growth Factors

There are only a few experimental studies which have investigated effects of glucose alone, and glucose in combination with insulin/insulin-like growth factors (IGF) on the growth of colon cancer. In the present study, we studied in vitro in human colorectal cancer cells originating from four Dukes’ stages of colorectal cancer the effects of glucose, insulin and IGFs on proliferation, migration, cell cycle progression and gene expression of the IGF system. Growth of colon cancer cells originating from a Dukes’ stage A was glucose-dependent, whereas growth of cancer cells from Dukes’ stage B, C and D was glucose-independent. Stimulatory effects of insulin and IGFs on cell growth were observed only in colon cancer cells originating from Dukes’ stage C and D. IGF-II stimulated migration in Dukes’ stage B cells only. The growth stimulatory effects in Dukes’ stage C and D colorectal cancer cells were accompanied by G2/M arrest and associated with an increased IGF-IR/IGF-II receptor ratio. In conclusion, our in vitro data suggest that the stimulating effects of glucose, IGFs and insulin on proliferation differ between colorectal cancer cells from early and late Dukes’ stages. Stimulatory effects of glucose on proliferation appear predominantly present in stage Dukes’ stage A colorectal cancer cells, while in contrast growth factor-mediated stimulation of cell proliferation is more pronounced in Dukes’ late stage (metastasized) colorectal cancer cells. Moreover, our study suggests that a stringent glucose control may be important to control tumor growth in early stages of colorectal cancer, while inhibition of the endocrine actions of the IGFs and insulin become more important in the late (metastasized) stages of colorectal cancer to restrain growth of colon cancer cells.

scholarly journals Dual Drug Targeting to Kill Colon Cancer Cells

2021 ◽  
Author(s):  
Antony W Burgess ◽  
Maree C Faux ◽  
Silvia Paola Corona ◽  
Janet Weinstock ◽  
Guillaume Lessene ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Xenograft Model ◽  
Specific Inhibitor ◽  
Colon Cancer Cells ◽  
Colon Adenomas ◽  
Mouse Xenograft Model ◽  
Signaling Inhibitors

Colorectal cancer (CRC) is driven by a small set of oncogenic and tumor suppressor mutations. However, different combinations of mutations often lead to poor tumor responses to individual anti-cancer drugs. We have investigated the anti-proliferative and in vitro cytotoxic activity of pair-wise combinations of inhibitors which target specific signaling pathways. Colon cancer cells in non-adherent cultures were killed more effectively by combinations of pyrvinium pamoate (a Wnt pathway inhibitor) and ABT263 (a pro-apoptotic Bcl-2 family inhibitor) or Ly29004 (a PI3kinase inhibitor). However, in a mouse xenograft model, the formulation and toxicity of the ABT737/PP combination prevent the use of these drugs for treatment of tumors. Fortunately, oral analogues of PP (pyrvinium phosphate, PPh) and ABT737(ABT263) have equivalent activity and can be used for treatment of mice carrying SW620 colorectal cancer xenografts. The PPh/ABT263 induced SW620 tumor cell apoptosis and reduced the rate of SW620 tumor growth. Combinations of Wnt signaling inhibitors and specific inhibitor of pro-survival proteins should be considered for the treatment of precancerous colon adenomas and advanced colorectal cancers with APC mutations.

scholarly journals MiR-34b inhibits the proliferation and promotes apoptosis in colon cancer cells by targeting Wnt/β-catenin signaling pathway

2019 ◽  
Vol 39 (10) ◽  
Author(s):  
Kailun Ye ◽  
Chunhua Xu ◽  
Tongguan Hui
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Human Colon ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Tumor Tissues

Abstract Colon cancer is one of the leading cause of cancer deaths that is severely threatening human health. Several microRNAs (miRNAs) have been found to be associated with the tumor genesis of colon cancer. The present study determined the expression of miR-34b in patients with colon cancer and studied the molecular mechanism of miR-34b in the proliferation and apoptosis of human colon cancer Caco-2 cells in vitro. In colon cancer patients, the expression of miR-34b was decreased in tumor tissues when compared with the adjacent non-tumor tissues. Furthermore, overexpression of miR-34b inhibited proliferation, migration and invasion, while promoted apoptosis in colon cancer cells. The online bioinformatics sites predicted possible regulatory genes of miR-34b and luciferase reporter assay verify that β-catenin was a direct target of miR-34b. Furthermore, miR-34b overexpression significantly decreased the expression of genes associated with Wnt/β-catenin signaling pathway. In conclusion, our results suggest that miR-34b may inhibit migration and invasion of human colon cancer cells by regulating Wnt/β-catenin signaling and miR-34b may be a key target for the treatment and diagnosis of colon cancer.

scholarly journals ID: 1036 FAM134B, a new player in human colorectal cancer pathogenesis

2017 ◽  
Vol 4 (S) ◽  
pp. 113
Author(s):  
Farhadul Islam ◽  
Vinod Gopalan ◽  
Alfred K-Y Lam
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Promoter Methylation ◽  
Colon Cancer Cells ◽  
Functional Roles ◽  
Cancer Pathogenesis ◽  
Cancer Tissues ◽  
Xenotransplantation Model

Background: FAM134B (family with sequence similarity 134, member B) is a relatively new player in many human diseases including cancers. In colorectal carcinomas, FAM134B plays important role in the pathogenesis and associated with biological aggressiveness of the disease. However, expression pattern, the frequency of mutations, methylation status in colon cancer cells and tissue samples has never been studied. Also, the functional roles of FAM134B in cell have never been studied in colorectal cancer. Objectives: To investigate FAM134B promoter methylation, mutations in tissues samples from patients with colorectal cancer and cell lines. Also, promoter methylation, expression and functional roles of FAM134B in colon cancer were studied.  Methods: Methylation and mutations in FAM134B sequence in cancer tissues (n=126) and matched non-cancer samples was studied by high-resolution melt curve analysis followed by Sanger sequencing. FAM134B expression was studied and quantified in cell lines and cancer tissues samples using immunofluorescence, immunocytochemistry, Western blot and real time PCR. In vitro functional assays and mouse xenotransplantation model were performed to unveil the molecular roles of FAM134B in colon cancer pathogenesis followed by shRNA-mediated silencing in cells.  Results: We noted that 46.5% (41/88) patients with colorectal cancer were identified as FAM134B mutations positive. Thirty-one novel pathogenic mutations were detected and these mutations were associated with gender of the patients, presence of metachronous cancer, size, T staging, presence of distant metastases and positivity of microsatellite instability (MSI) in the cancer (p < 0.05). Majority of cancer tissues had shown promoter hyper-methylation and were correlated with reduced mRNA and protein expression in both cancer samples and cells. FAM134B expression in cancer cells derived from advanced stages (stage III; SW48 and stage IV; HCT116) of colon cancer was significantly (p<0.01) reduced when compared to non-neoplastic colon cells (FHC) and cancer cells derived from stage II colon cancer (SW480). Expression of FAM134B mRNA in cancer tissues was noted significantly (p<0.001) downregulated when compared to that of non-cancer tissues samples. FAM134B suppression significantly (p<0.05) increased the proliferation of colon cancer cells, remarkably increased (3452% ; p<0.05) the clonogenic, migration capacity, and increases the proportion of cells in S phase of cell cycle (p<0.01). Xenotransplantation model showed that larger and higher grade tumors were formed in mice treated with FAM134B knockdown cells. Conclusion: Reduced expression in cancer samples, in vitro and in vivo functional studies implied that FAM134B acts as a cancer inhibitor in colon cancer play important roles in colorectal carcinogenesis.

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