scholarly journals Polygonum Barbatum Extract Reduces Colorectal Cancer Cell Proliferation, Migration, Invasion, and Epithelial-mesenchymal Transition via Regulation of the YAP and β-catenin Pathways

2021 ◽  
Author(s):  
Pi-Kai Chang ◽  
I-Chuan Yen ◽  
Wei-Cheng Tsai ◽  
Shih-Yu Lee
Keyword(s):  
Extracellular Matrix ◽  
Cell Growth ◽  
Cancer Cell ◽  
Colony Formation ◽  
Epithelial Mesenchymal Transition ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Pathway Enrichment Analysis ◽  
Human Colon Cancer ◽  
Mesenchymal Transition

Abstract BackgroundColorectal cancer (CRC) is the third most common cancer worldwide, but the development of novel therapeutics for CRC remains a challenge. Polygonum barbatum has anticancer potential, but its mechanism of action requires further investigation. This study was designed to investigate the inhibitory effect of Polygonum barbatum on human CRC cells. The HPLC fingerprints of the Polygonum barbatum extract (PBE) and quercetin standard were determined using analytical RP-HPLC and evaluations were completed using the human colon cancer cell line HCT-116 (KRASG13D mutation) and HT-29 cells. After treatment with PBE, cell viability, colony formation, migration, invasion, and apoptosis were analyzed using CCK-8, colony formation, wound healing, Transwell invasion, and flow cytometry assays, respectively. RNA-sequencing, western blotting, and co-immunoprecipitation were also used to analyze changes in the whole-transcriptome of these cells and identify possible mechanisms of action for PBE in CRC cells. ResultsPBE significantly reduced CRC cell growth, migration, and invasion, and Gene Ontology analysis showed that the genes responsible for extracellular matrix organization, cell motility, and cell growth were suppressed by PBE. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the differentially expressed genes revealed that PBE treatment exerted a significant effect on the extracellular matrix interaction and focal adhesion pathways. Consistently, epithelial-to-mesenchymal transition markers, including N-cadherin, vimentin, SLUG, and SNAIL, were also all shown to be regulated by PBE. These effects were associated with blockade of the Yes-associated protein and the GSK3β/β-catenin axis.ConclusionPolygonum barbatum extract exerts a significant inhibitory effect on CRC cells and may be potentially applicable in clinical trials.

scholarly journals Epigallocatechin-3-Gallate (EGCG) Suppresses Pancreatic Cancer Cell Growth, Invasion, and Migration partly through the Inhibition of Akt Pathway and Epithelial–Mesenchymal Transition: Enhanced Efficacy when Combined with Gemcitabine

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1856 ◽  
Author(s):  
Wei ◽  
Penso ◽  
Hackman ◽  
Wang ◽  
Mackenzie
Keyword(s):  
Pancreatic Cancer ◽  
Cell Growth ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Cancer Cell Growth ◽  
Mesenchymal Transition

Most pancreatic cancers are usually diagnosed at an advanced stage when they have already metastasized. Epigallocatechin-3-gallate (EGCG), a major polyphenolic constituent of green tea, has been shown to reduce pancreatic cancer growth, but its effect on metastasis remains elusive. This study evaluated the capacity of EGCG to inhibit pancreatic cancer cell migration and invasion and the underlying mechanisms. EGCG reduced pancreatic cancer cell growth, migration, and invasion in vitro and in vivo. EGCG prevented “Cadherin switch” and decreased the expression level of TCF8/ZEB1, β-Catenin, and Vimentin. Mechanistically, EGCG inhibited the Akt pathway in a time-dependent manner, by suppressing IGFR phosphorylation and inducing Akt degradation. Co-treatment with catalase or N-Acetyl-L-cysteine did not abrogate EGCG’s effect on the Akt pathway or cell growth. Moreover, EGCG synergized with gemcitabine to suppress pancreatic cancer cell growth, migration, and invasion, through modulating epithelial–mesenchymal transition markers and inhibiting Akt pathway. In summary, EGCG may prove beneficial to improve gemcitabine sensitivity in inhibiting pancreatic cancer cell migration and invasion, to some extent through the inhibition of Akt pathway and epithelial–mesenchymal transition.

scholarly journals Gemifloxacin, a Fluoroquinolone Antimicrobial Drug, Inhibits Migration and Invasion of Human Colon Cancer Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Jung-Yu Kan ◽  
Ya-Ling Hsu ◽  
Yen-Hsu Chen ◽  
Tun-Chieh Chen ◽  
Jaw-Yuan Wang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Migration ◽  
Nuclear Translocation ◽  
Epithelial Mesenchymal Transition ◽  
Human Colon ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Human Colon Cancer ◽  
Mesenchymal Transition ◽  
Cell Migration And Invasion

Gemifloxacin (GMF) is an orally administered broad-spectrum fluoroquinolone antimicrobial agent used to treat acute bacterial exacerbation of pneumonia and bronchitis. Although fluoroquinolone antibiotics have also been found to have anti-inflammatory and anticancer effects, studies on the effect of GMF on treating colon cancer have been relatively rare. To the best of our knowledge, this is the first report to describe the antimetastasis activities of GMF in colon cancer and the possible mechanisms involved. Results have shown that GMF inhibits the migration and invasion of colon cancer SW620 and LoVo cells and causes epithelial mesenchymal transition (EMT). In addition, GMF suppresses the activation of NF-κB and cell migration and invasion induced by TNF-αand inhibits the TAK1/TAB2 interaction, resulting in decreased IκB phosphorylation and NF-κB nuclear translocation in SW620 cells. Furthermore, Snail, a critical transcriptional factor of EMT, was downregulated after GMF treatment. Overexpression of Snail by cDNA transfection significantly decreases the inhibitory effect of GMF on EMT and cell migration and invasion. In conclusion, GMF may be a novel anticancer agent for the treatment of metastasis in colon cancer.

scholarly journals Src-1 and SP2 promote the proliferation and epithelial–mesenchymal transition of nasopharyngeal carcinoma

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 1061-1069
Author(s):  
Jingjing Zhang ◽  
Yuanyuan Yang ◽  
Hongyu Liu ◽  
Hongyi Hu
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Cell Viability ◽  
Colony Formation ◽  
Epithelial Mesenchymal Transition ◽  
Southern China ◽  
Mrna Level ◽  
Migration And Invasion ◽  
High Morbidity ◽  
Mesenchymal Transition ◽  
Steroid Receptor Coactivator

Abstract Nasopharyngeal carcinoma (NPC) is characterized by high morbidity and morality, especially in Southern China. Transcription factors intensively participate in the initiation and development of NPC. This study aimed to investigate the roles of Src-1 in NPC. mRNA level was determined by qRT-PCR. Western blot was carried out for the protein level. CCK-8 assay was performed to determine cell viability, colony formation for NPC cell proliferation, and transwell for cell migration and invasion ability. The results showed Steroid receptor coactivator 1 (Src-1) was overexpressed in SNE-2 and 6-10B. The expression of Src-1 and SP2 was in positive correlation. Overexpression of Src-1 promoted the cell viability, colony formation, and epithelial–mesenchymal transition (EMT), manifested by the increase of migration and invasion ability, while knockdown of Src-1 exerted opposite effects. Additionally, knockdown or overexpression of SP2 reversed the effects of overexpressed or downregulated Src-1, which was reversed by the depletion of SP2. Moreover, Src-1 interacted with SP2 to regulate EMT-related genes such as E-cad, N-cad, Vimentin, and ZEB1, and proliferation- and apoptosis-related genes, such as bax, cytochrome c, and cleaved caspase3 and bcl-2. Thus, blocking the interaction between Src-1 and SP2 may be a therapeutic target for inhibiting the metastasis of NPC.

scholarly journals Keratin 17 Suppresses Cell Proliferation and Epithelial-Mesenchymal Transition in Pancreatic Cancer

2020 ◽  
Vol 7 ◽  
Author(s):  
Yong Zeng ◽  
Min Zou ◽  
Yan Liu ◽  
Keting Que ◽  
Yunbing Wang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Cell Cycle Progression ◽  
Pancreatic Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation ◽  
Cycle Progression ◽  
Mesenchymal Transition

Keratin 17 (K17), a member of type I acidic epithelial keratin family, has been reported to be upregulated in many malignant tumors and to be involved in promoting the development of tumors. However, the precise role of K17 in progression of pancreatic cancer is still unknown. In this study, we found that K17 expression was highly expressed in pancreatic cancer tissues and cell lines and that upregulated expression was associated with the pathological grade and poor prognosis. K17 expression served as an independent predictor of pancreatic cancer survival. Meanwhile, we showed that knocking down K17 induced pancreatic cancer cell proliferation, colony formation and tumor growth in xenografts in mice. However, K17 upregulation inhibited pancreatic cancer cell proliferation and colony formation. Further mechanistic study revealed that K17 knockdown promoted cell cycle progression by upregulating CyclinD1 expression and repressed cell apoptosis. However, K17 upregulation suppressed cell cycle progression by decreasing CyclinD1 expression, and induced apoptosis by increasing the levels of cleaved Caspase3. In addition, K17 knockdown promoted pancreatic cancer cell migration and invasion, but K17 upregulation suppressed cell migration and invasion. Moreover, knocking down K17 promoted epithelial-mesenchymal transition (EMT) in pancreatic cancer cell by inhibiting E-cadherin expression and inducing Vimentin expression, and the effects of K17 upregulation were opposite to that of K17downregulation. Taken together, our findings suggest that K17 functions as a potential tumor suppressor, even though it is upregulated in pancreatic cancer.

scholarly journals Apigenin inhibits epithelial-mesenchymal transition of human colon cancer cells through NF-κB/Snail signaling pathway

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Jiafeng Tong ◽  
Ying Shen ◽  
Zhenghua Zhang ◽  
Ye Hu ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Transcription Factors ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Human Colon ◽  
Migration And Invasion ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Mesenchymal Transition ◽  
Human Colon Cancer Cells

Abstract Colon cancer is a leading cause of cancer-related deaths worldwide. The epithelial-mesenchymal transition (EMT) plays an important role in tumor metastasis of colon cancer. We first evaluated the effects of EMT-related transcription factors on the prognosis of colon cancer through analysis the data obtained from The Cancer Genome Atlas (TCGA). And then we screened a series of Chinese medicine monomers to find effect EMT inhibitors. First, Snail is a more important EMT transcription factors for colon cancer prognosis, compared with Twist and Slug. Then, we found that apigenin effectively inhibits the activity of Snail. Apigenin could inhibit the EMT, migration, and invasion of human colon cancer cells in vitro and in vivo through the NF-κB/Snail pathway. Snail is a key regulator of EMT in colon cancer and Snail inhibitor apigenin may be a therapeutic application for patients with colon cancer.

scholarly journals Inhibition to Epithelial-Mesenchymal Transition and Metastatic Potential In Colorectal Cancer Cell By Combination of Traditional Chinese Medicine Formulation Jiedu Sangen Decoction and PD-L1 Inhibitor

2020 ◽  
Vol 19 ◽  
pp. 153473542097248
Author(s):  
Feiyu Shan ◽  
Leitao Sun ◽  
Leyin Zhang ◽  
Kaibo Guo ◽  
Qingying Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Laser Scanning Microscopy ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Mesenchymal Transition

Background: Jiedu Sangen Decoction (JSD), a traditional Chinese medicine formula, has been widely applied in the treatment of gastrointestinal cancer, especially in colorectal cancer. Our study mainly aimed to assess the combined efficacy of Jiedu Sangen aqueous extract (JSAE) and a PD-L1 inhibitor (PI) in colon cancer cells migration and invasion, along with epithelial-mesenchymal transition, and then provide deep insights into the potential mechanism. Methods: We explored the inhibitory effects on invasion and metastasis and the reverse effect on EMT process in CT-26 colon cancer cell via Transwell migration assay, Matrigel invasion assay and confocal laser scanning microscopy. Furthermore, regulation in expression of EMT-related proteins and molecular biomarkers and underlying signal pathway proteins were detected through Western blotting and IHC. Results: The combination of JSD and PD-L1 inhibitor could inhibit migration, invasive ability and EMT of CT-26 cells in a concentration-dependent manner. Meanwhile, JSD combined with PD-L1 inhibitor could also remarkably reverse EMT and metastasis in vivo. In addition, the protein expression of N-cadherin, Slug, Snail, Vimentin was down-regulated along with E-cadherin s up-regulation with the combination of JSD and PD-L1 inhibitor, while that of PI3K/AKT was notably down-regulated. Conclusions: These findings indicated that JSAE and a PD-L1 inhibitor could drastically inhibit the migration and invasion of colorectal cancer by reversing EMT through the PI3K/AKT signaling pathway.

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