scholarly journals Oxidative Distress Induces Wnt/β-Catenin Pathway Modulation in Colorectal Cancer Cells: Perspectives on APC Retained Functions

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6045
Author(s):  
Teresa Catalano ◽  
Emira D’Amico ◽  
Carmelo Moscatello ◽  
Maria Carmela Di Marcantonio ◽  
Alessio Ferrone ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Cancer Recurrence ◽  
Tissue Microenvironment ◽  
Gene And Protein Expression ◽  
Colorectal Cancer Cells ◽  
Multistep Process ◽  
Sw620 Cells ◽  
Apc Protein ◽  
Relationship Of

Colorectal cancer (CRC) is a multistep process that arises in the colic tissue microenvironment. Oxidative stress plays a role in mediating CRC cell survival and progression, as well as promoting resistance to therapies. CRC progression is associated with Wnt/β-Catenin signaling dysregulation and loss of proper APC functions. Cancer recurrence/relapse has been attributed to altered ROS levels, produced in a cancerous microenvironment. The effect of oxidative distress on Wnt/β-Catenin signaling in the light of APC functions is unclear. This study evaluated the effect of H2O2-induced short-term oxidative stress in HCT116, SW480 and SW620 cells with different phenotypes of APC and β-Catenin. The modulation and relationship of APC with characteristic molecules of Wnt/β-Catenin were assessed in gene and protein expression. Results indicated that CRC cells, even when deprived of growth factors, under acute oxidative distress conditions by H2O2 promote β-Catenin expression and modulate cytoplasmic APC protein. Furthermore, H2O2 induces differential gene expression depending on the cellular phenotype and leading to favor both Wnt/Catenin-dependent and -independent signaling. The exact mechanism by which oxidative distress can affect Wnt signaling functions will require further investigation to reveal new scenarios for the development of therapeutic approaches for CRC, in the light of the conserved functions of APC.

scholarly journals Calcium Channel Protein ORAI1 Mediates TGF-β Induced Epithelial-to-Mesenchymal Transition in Colorectal Cancer Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Qingjie Kang ◽  
Xudong Peng ◽  
Xiangshu Li ◽  
Denghua Hu ◽  
Guangxu Wen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Calcium Channel ◽  
Cancer Cells ◽  
Transforming Growth Factor ◽  
Mesenchymal Transition ◽  
Colorectal Cancer Cells ◽  
Sw480 Cells ◽  
Sw620 Cells ◽  
Tgf Β1

Accumulating evidence suggested that calcium release-activated calcium modulator 1(ORAI1), a key calcium channel pore-forming protein-mediated store-operated Ca2+ entry (SOCE), is associated with human cancer. However, its role in colorectal cancer (CRC) progression has not been well studied. Epithelial-mesenchymal transition (EMT) is a multistep process that occurs during the progression of cancers and is necessary for metastasis of epithelial cancer. Transforming growth factor-β (TGF-β) is a pleiotropic cytokine that has been shown to induce EMT. In this study, we are aimed at exploring the effects of ORAI1 on TGF-β1-induced EMT process in CRC cells. Herein, we confirmed ORAI1 expression was higher in CRC tissues than in adjacent non-cancerous tissues by using immunohistochemical staining and Western blot analysis. Higher ORAI1 expression was associated with more advanced clinical stage, higher incidence of metastasis and shorter overall survival. We compared ORAI1 expression in SW480 and SW620 cells, two CRC cell lines with the same genetic background, but different metastatic potential. We found ORAI1 expression was significantly higher in SW620 cells which exhibited higher EMT characteristics. Furthermore, knockdown of ORAI1 suppressed the EMT of SW620 Cells. After induced the EMT process in SW480 cells with TGF-β1, we found treatment of TGF-β1 showed a significant increase in cell migration along with the loss of E-cadherin and an increase in N-cadherin and Vimentin protein levels. Also, TGF-β1 treatment increased ORAI1 expression and was closely associated with the increase of SOCE. Silencing ORAI1 significantly suppressed Ca2+ entry, reversed the changes of EMT-relevant marks expression induced by TGF-β1, and inhibited TGF-β1-mediated calpain activation and cell migration. Finally, we blocked SOCE with 2-APB (2-Aminoethyl diphenylborinate), a pharmacological inhibitor. Interestingly, 2-APB and sh-ORAI1 both exhibited similar inhibition effects to the SW480 cells. In conclusion, our results demonstrated that ORAI1 could mediate TGF-β-Induced EMT by promoting Ca2+ entry and calpain activity in Colorectal Cancer Cells.

scholarly journals LncRNA CRNDE Promoted Colorectal Cancer Cells Reisitance To Paclitaxel Through Wnt/β-Catenin Signaling Pathway

2021 ◽  
Author(s):  
Rui Ma ◽  
Chuan-yang Yu ◽  
Xiang Tao ◽  
Zhi Yang ◽  
Qi Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Colorectal Neoplasia ◽  
Cancer Treatments ◽  
Sw620 Cell ◽  
Invasion And Migration ◽  
Over Expression ◽  
Colorectal Cancer Cells ◽  
Sw620 Cells ◽  
And Migration

Abstract Background The lncRNA colorectal neoplasia differentially expressed (lncRNA CRNDE) is commonly over-expressed in different human cancers and involved in different biological functions. Paclitaxel(PTX) is a tricyclic diterpenoid compound which often used as a natural anticancer drugs in cancer treatments. Although there have many research reports about the mechanisms of LncRNA involved in PTX treatment, there are no any research about lncRNA CRNDE and PTX resistance in colorectal cancer. The purpose of this study is to investigate the mechanisims of LncRNA CRNDE involving PTX resistance in colorectal cancer. Results We constructed lncRNA CRNDE over-expression vector and transfected it into SW620 cell. CCK8, Transwell experiments proved that over-expression of lnc CRNDE increased SW620 cells proliferation and invasion, while the si-CRNDE group was significantly decreased. over-expression CRNDE can significantly up-regulate β-catenin, c-myc, APC and Axin2 expression and affect the expression of cyclinD1 and CDK4 after treated with PTX. Conclusion lncRNA CRNDE promotes CRCs proliferation, invasion and migration. Over-expression of LncRNA CRNDE enhanced the reisitance of CRC to PTX through inhibition of Wnt/ β-catenin signaling pathway.

CircABCC4 Regulates the Proliferation, Migration, and Invasion of Colorectal Cancer SW620 Cells by Targeting Micro RNA-216a-3p

2021 ◽  
Vol 11 (3) ◽  
pp. 548-552
Author(s):  
Yiqian Li ◽  
Haofeng Yuan ◽  
Yibin Chen ◽  
Baoqi Xu ◽  
Yanhong Zhang
Keyword(s):  
Colorectal Cancer ◽  
Micro Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Human Colorectal Cancer ◽  
Cell Behaviors ◽  
Colorectal Cancer Cells ◽  
Sw620 Cells ◽  
Cancer Tissues ◽  
Dual Luciferase Reporter Assay

This work investigates the effect of circABCC4 on the proliferation, migration, and invasion of colorectal cancer SW620 cells; circABCC4’s regulation of miR-216a-3p is also studied. qRT-PCR was used to measure the levels of circABCC4 and miR-216a-3p in colorectal cancer and adjacent tissues. The human colorectal cancer SW620 cells were transfected with different constructs of circABCC4 or miR-216a-3p or both to study their interactions and combined effects on cell behavior. A dual-luciferase reporter experiment tested the targeted relationship between circABCC4 to miR-216a-3p. Furthermore, the behaviors of SW620 cells, such as cell viability, migration, and invasion, were investigated. Also, the proteins related to cell behaviors were investigated with western blotting. Our results showed that colorectal cancer tissues had a higher level of circABCC4 but a lower level miR-216a-3p. The increased level of circABCC4 and the reduced level of miR-216a-3p had analogous influences on the behaviors of SW620 cells, resulting in reduced cell proliferation, migration, and invasion; the levels of related protein were also decreased. Moreover, we found that disrupting miR-548c-3p could reverse the influence of inhibiting circABCC4 on SW620 cells. In addition, the dual-luciferase reporter assay results confirmed the targeting of miR-216a-3p by circABCC4. These data demonstrate that the silencing of circABCC4 may inhibit the proliferation, migration, and invasion of colorectal cancer cells by upregulating miR-548c-3p.

scholarly journals Identification of Two Kinase Inhibitors with Synergistic Toxicity with Low-Dose Hydrogen Peroxide in Colorectal Cancer Cells In vitro

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 122 ◽  
Author(s):  
Eric Freund ◽  
Kim-Rouven Liedtke ◽  
Lea Miebach ◽  
Kristian Wende ◽  
Amanda Heidecke ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Hydrogen Peroxide ◽  
Protein Kinase ◽  
Tumor Cells ◽  
Low Dose ◽  
Kinase Inhibitors ◽  
Protein Kinase Inhibitors ◽  
Colorectal Cancer Cells

Colorectal carcinoma is among the most common types of cancers. With this disease, diffuse scattering in the abdominal area (peritoneal carcinosis) often occurs before diagnosis, making surgical removal of the entire malignant tissue impossible due to a large number of tumor nodules. Previous treatment options include radiation and its combination with intraperitoneal heat-induced chemotherapy (HIPEC). Both options have strong side effects and are often poor in therapeutic efficacy. Tumor cells often grow and proliferate dysregulated, with enzymes of the protein kinase family often playing a crucial role. The present study investigated whether a combination of protein kinase inhibitors and low-dose induction of oxidative stress (using hydrogen peroxide, H2O2) has an additive cytotoxic effect on murine, colorectal tumor cells (CT26). Protein kinase inhibitors from a library of 80 substances were used to investigate colorectal cancer cells for their activity, morphology, and immunogenicity (immunogenic cancer cell death, ICD) upon mono or combination. Toxic compounds identified in 2D cultures were confirmed in 3D cultures, and additive cytotoxicity was identified for the substances lavendustin A, GF109203X, and rapamycin. Toxicity was concomitant with cell cycle arrest, but except HMGB1, no increased expression of immunogenic markers was identified with the combination treatment. The results were validated for GF109203X and rapamycin but not lavendustin A in the 3D model of different colorectal (HT29, SW480) and pancreatic cancer cell lines (MiaPaca, Panc01). In conclusion, our in vitro data suggest that combining oxidative stress with chemotherapy would be conceivable to enhance antitumor efficacy in HIPEC.

Oxidative stress causes epigenetic alteration of CDX1 expression in colorectal cancer cells

Gene ◽  
2013 ◽  
Vol 524 (2) ◽  
pp. 214-219 ◽  
Author(s):  
Rui Zhang ◽  
Kyoung Ah Kang ◽  
Ki Cheon Kim ◽  
Soo-Young Na ◽  
Weon Young Chang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Cancer Cells ◽  
Epigenetic Alteration ◽  
Colorectal Cancer Cells

scholarly journals Zerumbone increases oxidative stress in a thiol‐dependent ROS ‐independent manner to increase DNA damage and sensitize colorectal cancer cells to radiation

2014 ◽  
Vol 4 (2) ◽  
pp. 278-292 ◽  
Author(s):  
Amit Deorukhkar ◽  
Niharika Ahuja ◽  
Armando‐Lopez Mercado ◽  
Parmeswaran Diagaradjane ◽  
Uma Raju ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Independent Manner ◽  
Colorectal Cancer Cells

scholarly journals Alpha-Glucosidase Inhibitor Voglibose Suppresses Azoxymethane-Induced Colonic Preneoplastic Lesions in Diabetic and Obese Mice

2020 ◽  
Vol 21 (6) ◽  
pp. 2226 ◽  
Author(s):  
Junichi Kato ◽  
Yohei Shirakami ◽  
Taku Mizutani ◽  
Masaya Kubota ◽  
Hiroyasu Sakai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Insulin Resistance ◽  
Growth Factor ◽  
Cancer Cells ◽  
Insulin Like Growth Factor ◽  
Glucosidase Inhibitor ◽  
Colorectal Cancer Cells ◽  
Neoplastic Lesions ◽  
Alpha Glucosidase

Type 2 diabetes mellitus and its related insulin resistance are known to increase the risk of cancer. Anti-diabetic agents can improve insulin resistance and may lead to the suppression of carcinogenesis. This study aimed to investigate the preventive effects of the alpha-glucosidase inhibitor voglibose on the development of azoxymethane-induced colorectal pre-neoplastic lesions in obese and diabetic C57BL/KsJ-db/db mice. The direct effects of voglibose on the proliferation of colorectal cancer cells were also evaluated. Mice were injected with azoxymethane to induce colorectal pre-malignancy and were then administered drinking water with or without voglibose. At the end of the study, the administration of voglibose significantly suppressed the development of colorectal neoplastic lesions. In voglibose-treated mice, serum glucose levels, oxidative stress, as well as mRNA expression of the insulin-like growth factor-1 in the colon mucosa, were reduced. The proliferation of human colorectal cancer cells was not altered by voglibose. These results suggested that voglibose suppressed colorectal carcinogenesis in a diabetes- and obesity-related colorectal cancer model, presumably by improving inflammation via the reduction of oxidative stress and suppressing of the insulin-like growth factor/insulin-like growth factor-1 receptor axis in the colonic mucosa.

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