scholarly journals Manzamine A Exerts Anticancer Activity against Human Colorectal Cancer Cells

Marine Drugs ◽  
2018 ◽  
Vol 16 (8) ◽  
pp. 252 ◽  
Author(s):  
Li-Chun Lin ◽  
Tzu-Ting Kuo ◽  
Hsin-Yi Chang ◽  
Wen-Shan Liu ◽  
Shih-Min Hsia ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Anticancer Activity ◽  
Epithelial Mesenchymal Transition ◽  
Apoptotic Cell ◽  
Transition Process ◽  
Marine Sponges ◽  
Manzamine A ◽  
Mesenchymal Transition ◽  
Starting Point

Marine sponges are known to produce numerous bioactive secondary metabolites as defense strategies to avoid predation. Manzamine A is a sponge-derived β-carboline-fused pentacyclic alkaloid with various bioactivities, including recently reported anticancer activity on pancreatic cancer. However, its cytotoxicity and mode of action against other tumors remain unclear. In this study, we exhibit that manzamine A reduced cell proliferation in several colorectal cancer (CRC) cell lines. To further investigate the manzamine A triggered molecular regulation, we analyzed the gene expression with microarray and revealed that pathways including cell cycle, DNA repair, mRNA metabolism, and apoptosis were dysregulated. We verified that manzamine A induced cell cycle arrest at G0/G1 phase via inhibition of cyclin-dependent kinases by p53/p21/p27 and triggered a caspase-dependent apoptotic cell death through mitochondrial membrane potential depletion. Additionally, we performed bioinformatics analysis and demonstrated that manzamine A abolished epithelial–mesenchymal transition process. Several mesenchymal transcriptional factors, such as Snail, Slug, and Twist were suppressed and epithelial marker E-cadherin was induced simultaneously in HCT116 cells by manzamine A, leading to the epithelial-like phenotype and suppression of migration. These findings suggest that manzamine A may serve as a starting point for the development of an anticancer drug for the treatment of metastatic CRC.

scholarly journals PPTS Inhibits the TGF-β1-Induced Epithelial-Mesenchymal Transition in Human Colorectal Cancer SW480 Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Ling Zhang ◽  
Abid Naeem ◽  
Shaofeng Wei ◽  
Zexie Li ◽  
Zhenzhong Zang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Research Work ◽  
Human Colorectal Cancer ◽  
Migration Ability ◽  
Triterpenoid Saponins ◽  
Mesenchymal Transition ◽  
Sw480 Cells

The current study investigates the inhibitory effects of Pulsatilla pentacyclic triterpenoid saponins extract (PPTS) on epithelial-mesenchymal transition (EMT) triggered by the transforming growth factor-β1 (TGF-β1) in human colorectal cancer SW480 cell line, further illustrates the possible mechanism of PPTS inhibition of growth and invasion from the perspective of EMT, and provides new theoretical support for the treatment of tumor by Chinese medicine. The SW480 cells were treated in groups: blank control, TGF-β1 (10 ng/mL), and varying concentrations of PPTS cotreated with TGF-β1-induced (10 ng/mL) groups. CCK8 was used to detect cell viability; transwell was applied to detect invasion ability, cell migration ability was also determined, ELISA and RT-qPCR were utilized for the determination of CYP3A, CYP2C9, CYP2C19, N-cadherin, and MMP-9 expression. Flow cytometry detection was applied to detect cell cycle and apoptosis. The results obtained have shown that PPTS can significantly inhibit the invasion and migration of tumors in SW480 cells and can also block the S phase in the cell cycle but may produce cytotoxicity in higher doses. The present research work provides substantial evidence that PPTS has a significant inhibitory effect on TGF-β1-induced EMT in SW480 cells and it also promotes apoptosis.

Elevated soluble E-cadherin during the epithelial-mesenchymal transition process and as a diagnostic marker in colorectal cancer

Gene ◽  
2020 ◽  
Vol 754 ◽  
pp. 144899
Author(s):  
Shuzhen Zhu ◽  
Guanghui Zhao ◽  
Xiaoyun Zhao ◽  
Xiaohong Zhan ◽  
Meijuan Cai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Diagnostic Marker ◽  
Transition Process ◽  
Mesenchymal Transition ◽  
E Cadherin

scholarly journals Circulating microRNA-762 upregulates colorectal cancer might through Wnt-1/β-catenin signaling

2020 ◽  
Author(s):  
Peng-Sheng Lai ◽  
Wei-Min Chang ◽  
Ying-Yin Chen ◽  
Yi-Feng Lin ◽  
Hui-Fen Liao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Viability ◽  
Distant Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Human Subjects ◽  
Circulating Microrna ◽  
High Concentration ◽  
Mesenchymal Transition ◽  
Cell Implantation

ABSTRACTBackgroundA number of microRNAs (miRNAs) have been demonstrated to be correlated with the diagnosis, progression and prognosis of colorectal cancer (CRC). However, the key miRNAs and the associated signaling pathways that regulate the growth and metastasis of CRC remain unclear.MethodsThe circulating miRNAs from BALB/c mice with CRC CT26 cell implantation were assayed by microarray. Then, mmu-miR-762 mimic and inhibitor were transfected to CT26 cells for analysis of cell viability, invasion, and epithelial-mesenchymal transition (EMT), cell cycle, and regulatory molecule expression. Human subjects were included for comparison the circulating has-miR-762 levels in CRC patients and control donors, as well as the patients with and without distant metastasis.ResultsThe miRNA levels in mice with CRC cell implantation indicated that plasma mmu-miR-762 was upregulated. Transfection of mmu-miR-762 mimic to CT26 cells increased cell viability, invasion, and EMT, whereas transfection of mmu-miR-762 inhibitor decreased the above abilities. Cells treated with high-concentration mmu-miR-762 inhibitor induced cell cycle arrest at G0/G1 phase. Western blot analysis showed that mmu-miR-762 mimic transfection upregulated the expression of Wnt-1 and β-catenin. Further analysis was performed to demonstrate the correlation of has-miR-762 with CRC patients. The results showed that serum has-miR-762 levels in CRC patients were higher than in control donors. Among the CRC patients, patients with distant metastasis showed higher serum has-miR-762 levels than patients without distant metastasis.ConclusionsThe present study demonstrated that circulating miR-762 might be a biomarker with upregulation of CRC cell growth and invasion through the Wnt/β-catenin signaling.

scholarly journals Curcumin inhibits epithelial-mesenchymal transition in colorectal cancer cells by regulating miR-206/SNAI2 pathway

2021 ◽  
Vol 18 (7) ◽  
pp. 1405-1412
Author(s):  
Pan Zhao ◽  
Chunjie Zhang ◽  
Dafei Xie ◽  
Maowei Pei
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Transition Process ◽  
Cellular Migration ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Reverse Transcription Pcr ◽  
Colorectal Cancer Cells

Purpose: To examine the effects of curcumin on epithelial-mesenchymal transition (EMT) via regulation of miR-206 and SNAI2 in colorectal cancer (CRC) cells. Relationship between SNAI2 and miR-206 and the effects of curcumin on related mechanisms were also identified. Methods: Transwell assays were used to analyze cellular migration and invasion. Genes associated with changes in protein and mRNA expression were evaluated by western blotting and quantitative reverse transcription PCR analyses, respectively. The relationship between SNAI2 and miR-206 was determined using a dual luciferase assay. Results: Curcumin inhibited cell metastasis, upregulated miR-206 expression, and decreased SNAI2 levels. Furthermore, miR-206 directly targeted SNAI2 and inhibited EMT via downregulation of SNAI2 expression. Curcumin inhibited EMT in CRC cells by upregulating miR-206. Conclusion: This study, for the first time, discovered the role of curcumin on epithelial-mesenchymal transition process in colorectal cancer cells by modulating miR-206/SNAI2 axis. These findings suggest that curcumin may be useful as a novel therapeutic agent to inhibit the metastasis of CRC.

scholarly journals A Comprehensive Bioinformatics Analysis of Notch Pathways in Bladder Cancer

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3089
Author(s):  
Chuan Zhang ◽  
Mandy Berndt-Paetz ◽  
Jochen Neuhaus
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Notch Signaling ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Biology ◽  
Disease Free Survival ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Notch Receptors ◽  
Notch Pathways

Background: A hallmark of Notch signaling is its variable role in tumor biology, ranging from tumor-suppressive to oncogenic effects. Until now, the mechanisms and functions of Notch pathways in bladder cancer (BCa) are still unclear. Methods: We used publicly available data from the GTEx and TCGA-BLCA databases to explore the role of the canonical Notch pathways in BCa on the basis of the RNA expression levels of Notch receptors, ligands, and downstream genes. For statistical analyses of cancer and non-cancerous samples, we used R software packages and public databases/webservers. Results: We found differential expression between control and BCa samples for all Notch receptors (NOTCH1, 2, 3, 4), the delta-like Notch ligands (DLL1, 3, 4), and the typical downstream gene hairy and enhancer of split 1 (HES1). NOTCH2/3 and DLL4 can significantly differentiate non-cancerous samples from cancers and were broadly altered in subgroups. High expression levels of NOTCH2/3 receptors correlated with worse overall survival (OS) and shorter disease-free survival (DFS). However, at long-term (>8 years) follow-up, NOTCH2 expression was associated with a better OS and DFS. Furthermore, the cases with the high levels of DLL4 were associated with worse OS but improved DFS. Pathway network analysis revealed that NOTCH2/3 in particular correlated with cell cycle, epithelial–mesenchymal transition (EMT), numbers of lymphocyte subtypes, and modulation of the immune system. Conclusions: NOTCH2/3 and DLL4 are potential drivers of Notch signaling in BCa, indicating that Notch and associated pathways play an essential role in the progression and prognosis of BCa through directly modulating immune cells or through interaction with cell cycle and EMT.

scholarly journals Epithelial-Mesenchymal Transition and MicroRNAs in Colorectal Cancer Chemoresistance to FOLFOX

Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 75
Author(s):  
Paula I. Escalante ◽  
Luis A. Quiñones ◽  
Héctor R. Contreras
Keyword(s):  
Colorectal Cancer ◽  
Tumor Cells ◽  
Methylenetetrahydrofolate Reductase ◽  
Epithelial Mesenchymal Transition ◽  
Late Onset ◽  
Dihydropyrimidine Dehydrogenase ◽  
Acquired Resistance ◽  
Potential Effect ◽  
Mesenchymal Transition ◽  
Folfox Chemotherapy

The FOLFOX scheme, based on the association of 5-fluorouracil and oxaliplatin, is the most frequently indicated chemotherapy scheme for patients diagnosed with metastatic colorectal cancer. Nevertheless, development of chemoresistance is one of the major challenges associated with this disease. It has been reported that epithelial-mesenchymal transition (EMT) is implicated in microRNA-driven modulation of tumor cells response to 5-fluorouracil and oxaliplatin. Moreover, from pharmacogenomic research, it is known that overexpression of genes encoding dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), the DNA repair enzymes ERCC1, ERCC2, and XRCC1, and the phase 2 enzyme GSTP1 impair the response to FOLFOX. It has been observed that EMT is associated with overexpression of DPYD, TYMS, ERCC1, and GSTP1. In this review, we investigated the role of miRNAs as EMT promotors in tumor cells, and its potential effect on the upregulation of DPYD, TYMS, MTHFR, ERCC1, ERCC2, XRCC1, and GSTP1 expression, which would lead to resistance of CRC tumor cells to 5-fluorouracil and oxaliplatin. This constitutes a potential mechanism of epigenetic regulation involved in late-onset of acquired resistance in mCRC patients under FOLFOX chemotherapy. Expression of these biomarker microRNAs could serve as tools for personalized medicine, and as potential therapeutic targets in the future.

B7-H4 induces epithelial–mesenchymal transition and promotes colorectal cancer stemness

2021 ◽  
pp. 153323
Author(s):  
Ying Feng ◽  
Zhaoting Yang ◽  
Chengye Zhang ◽  
Nan Che ◽  
Xingzhe Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Stemness ◽  
Mesenchymal Transition
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