scholarly journals Scaphium affine Ethanol Extract Induces Anoikis by Regulating the EGFR/Akt Pathway in HCT116 Colorectal Cancer Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Hye Won Kawk ◽  
Gun-He Nam ◽  
Myeong Jin Kim ◽  
Sang-Yong Kim ◽  
Young-Min Kim
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Hct116 Cell ◽  
Akt Pathway ◽  
Dependent Manner ◽  
Anticancer Effects ◽  
Colorectal Cancer Cells ◽  
Dose Dependent

Scaphium affine ethanol extracts (SAE) is a species that has been shown to contain various physiological effects; however, its anticancer effects have yet to be revealed. We qualitatively evaluated β-sitosterol in SAE through high-performance liquid chromatography (HPLC). The cytotoxicity in HCT116 and HT29 colorectal cancer cells and CCD841 normal colon cells was confirmed through WST-1 assays. Selective cytotoxicity was observed in colorectal cancer cells, with greater cytotoxicity demonstrated in the HCT116 cell line. As such, the HCT116 colorectal cell line was selected for subsequent experiments. After HCT116 cells were treated with SAE, it was confirmed that the apoptosis rate was increased in a SAE dose-dependent manner through Annexin V assay. SAE further showed dose-dependent suppression of invasion through invasion assays. Anoikis induction through the EGFR/Akt pathway in HCT116 colorectal cancer cells was confirmed by Western blotting. The tumor suppressive effects of SAE was assessed in vivo using a xenograft model of human HCT116 colorectal cancer cells. As a result, we confirmed that SAE decreased tumor size in a dose-dependent manner and that p-EGFR and cleaved-caspase 3 in tumors were also regulated in a dose-dependent manner. This study showed that SAE, by containing β-sitosterol with proven anticancer effects, induces anoikis through the EGFR/Akt pathway in HCT116 colorectal cancer cells both in vitro and in vivo.

scholarly journals TBX3 acts as tissue-specific component of the Wnt/β-catenin transcriptional complex

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Dario Zimmerli ◽  
Costanza Borrelli ◽  
Amaia Jauregi-Miguel ◽  
Simon Söderholm ◽  
Salome Brütsch ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Target Genes ◽  
Regulatory Elements ◽  
Dependent Manner ◽  
Independent Manner ◽  
Tissue Specific ◽  
Colorectal Cancer Cells ◽  
Transcriptional Complex

BCL9 and PYGO are β-catenin cofactors that enhance the transcription of Wnt target genes. They have been proposed as therapeutic targets to diminish Wnt signaling output in intestinal malignancies. Here we find that, in colorectal cancer cells and in developing mouse forelimbs, BCL9 proteins sustain the action of β-catenin in a largely PYGO-independent manner. Our genetic analyses implied that BCL9 necessitates other interaction partners in mediating its transcriptional output. We identified the transcription factor TBX3 as a candidate tissue-specific member of the β-catenin transcriptional complex. In developing forelimbs, both TBX3 and BCL9 occupy a large number of Wnt-responsive regulatory elements, genome-wide. Moreover, mutations in Bcl9 affect the expression of TBX3 targets in vivo, and modulation of TBX3 abundance impacts on Wnt target genes transcription in a β-catenin- and TCF/LEF-dependent manner. Finally, TBX3 overexpression exacerbates the metastatic potential of Wnt-dependent human colorectal cancer cells. Our work implicates TBX3 as context-dependent component of the Wnt/β-catenin-dependent transcriptional complex.

scholarly journals Silibinin Inhibits TGF-β-induced MMP-2 and MMP-9 Through Smad Signaling Pathway in Colorectal Cancer HT-29 Cells

2021 ◽  
Author(s):  
Zahra Zare ◽  
Tina Nayerpour dizaj ◽  
Armaghan Lohrasbi ◽  
Zakieh Sadat Sheikhalishahi ◽  
Amirhooman Asadi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cell Line ◽  
Dependent Manner ◽  
Smad2 Phosphorylation ◽  
Mrna And Protein Expression ◽  
Dose Dependent ◽  
Ht 29

Background: Metastasis of cancer cells is the primary responsible for death in patients with colorectal cancer (CRC). Transforming growth factor-β (TGF-β)-induced matrix metalloproteinases (MMPs) are essential for the metastasis process. Silibinin is a natural compound extracted from the Silybum marianum that exhibits anti-neoplastic activity in cancer cell lines. In this study, we evaluated the effects of silibinin on MMP-2 and MMP-9 induced by TGF-β in human HT-29 CRC cell line and the potential mechanism underlying the effects. Methods: The present in vitro study was done on the HT-29 cell line. The HT-29 cell line was cultured in RPMI1640 and exposed to TGF- β (5 ng/ml) in the absence and presence of different concentrations of silibinin (10, 25, 50, and 100 μM). The effect of silibinin on HT-29 cell viability was measured with the MTT assay. A real-time polymerase chain reaction (Real-Time PCR) determined the relative mRNA expression of MMP-2 and MMP-9. Western blotting was employed to examine MMP-2 and MMP 9 protein expression and Smad2 phosphorylation. Results: Silibinin inhibits cell viability of HT-29 cell line at 24 hours in a dose-dependent manner. TGF-β increased the mRNA and protein expression of MMP-2, MMP-9, and phosphorylated Smad2 compared to controls. Pharmacological inhibition with silibinin markedly blocked TGF-β–induced MMP-2 and MMP-9 mRNA and protein expression and Smad2 phosphorylation. Conclusion: Silibinin decreased the cell viability of HT-29 cancer cells in a dose-dependent manner. Silibinin also inhibited TGF-β-stimulated MMP-2 and MMP-9 expression in HT-29 cells, possibly mediated with the Smad2 signaling pathway.

scholarly journals TBX3 acts as tissue-specific component of the Wnt/β-catenin enhanceosome

2020 ◽  
Author(s):  
Dario Zimmerli ◽  
Costanza Borrelli ◽  
Amaia Jauregi-Miguel ◽  
Simon Söderholm ◽  
Salome Brütsch ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Target Genes ◽  
Metastatic Potential ◽  
Regulatory Elements ◽  
Dependent Manner ◽  
Independent Manner ◽  
Tissue Specific ◽  
Colorectal Cancer Cells

AbstractBCL9 and PYGO are β-catenin cofactors that enhance the transcription of Wnt target genes. They have been proposed as therapeutic targets to diminish Wnt signalling output in intestinal malignancies. Here we find that, in colorectal cancer cells and in developing mouse forelimbs, BCL9 proteins sustain the action of β-catenin in a largely PYGO-independent manner. Our genetic analyses implied that BCL9 necessitates other interaction partners in mediating its transcriptional output. We identified the transcription factor TBX3 as a candidate tissue-specific member of the β-catenin transcriptional complex. In developing forelimbs, TBX3 and BCL9 co-occupy a large number of Wnt-responsive regulatory elements, genome-wide. Moreover, mutations in Bcl9 affect the expression of TBX3 targets in vivo, and modulation of TBX3 abundance impacts on Wnt target genes transcription in a β-catenin- and TCF/LEF-dependent manner. Finally, TBX3 overexpression exacerbates the metastatic potential of Wnt-dependent human colorectal cancer cells. Our work implicates TBX3 as a new, context-dependent component of the Wnt/β-catenin-dependent enhanceosome.

scholarly journals Anticancer effects of Qizhen Capsule in human colorectal cancer cells in vitro and in vivo

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Dandan Guo ◽  
Chenjie Guo ◽  
Yujie Wang ◽  
Kaikai Wu ◽  
Liu Fang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Human Colorectal Cancer ◽  
Anticancer Effects ◽  
Colorectal Cancer Cells ◽  
Human Colorectal Cancer Cells

scholarly journals Decyl caffeic acid inhibits the proliferation of colorectal cancer cells in an autophagy-dependent manner in vitro and in vivo

PLoS ONE ◽  
2020 ◽  
Vol 15 (5) ◽  
pp. e0232832 ◽  
Author(s):  
Ching Chen ◽  
Yueh-Hsiung Kuo ◽  
Cheng-Chieh Lin ◽  
Che-Yi Chao ◽  
Man-Hui Pai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Caffeic Acid ◽  
Dependent Manner ◽  
Colorectal Cancer Cells

scholarly journals Dehydrodiisoeugenol inhibits colorectal cancer growth by endoplasmic reticulum stress-induced autophagic pathways

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Changhong Li ◽  
Kui Zhang ◽  
Guangzhao Pan ◽  
Haoyan Ji ◽  
Chongyang Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Endoplasmic Reticulum ◽  
Cell Growth ◽  
Er Stress ◽  
Cancer Cells ◽  
Tumor Xenograft ◽  
Anticancer Activities ◽  
Colorectal Cancer Cells

Abstract Background Dehydrodiisoeugenol (DEH), a novel lignan component extracted from nutmeg, which is the seed of Myristica fragrans Houtt, displays noticeable anti-inflammatory and anti-allergic effects in digestive system diseases. However, the mechanism of its anticancer activity in gastrointestinal cancer remains to be investigated. Methods In this study, the anticancer effect of DEH on human colorectal cancer and its underlying mechanism were evaluated. Assays including MTT, EdU, Plate clone formation, Soft agar, Flow cytometry, Electron microscopy, Immunofluorescence and Western blotting were used in vitro. The CDX and PDX tumor xenograft models were used in vivo. Results Our findings indicated that treatment with DEH arrested the cell cycle of colorectal cancer cells at the G1/S phase, leading to significant inhibition in cell growth. Moreover, DEH induced strong cellular autophagy, which could be inhibited through autophagic inhibitors, with a rction in the DEH-induced inhibition of cell growth in colorectal cancer cells. Further analysis indicated that DEH also induced endoplasmic reticulum (ER) stress and subsequently stimulated autophagy through the activation of PERK/eIF2α and IRE1α/XBP-1 s/CHOP pathways. Knockdown of PERK or IRE1α significantly decreased DEH-induced autophagy and retrieved cell viability in cells treated with DEH. Furthermore, DEH also exhibited significant anticancer activities in the CDX- and PDX-models. Conclusions Collectively, our studies strongly suggest that DEH might be a potential anticancer agent against colorectal cancer by activating ER stress-induced inhibition of autophagy.

scholarly journals Extract of Pogostemon cablin Possesses Potent Anticancer Activity against Colorectal Cancer Cells In Vitro and In Vivo

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Ju-Huei Chien ◽  
Shan-Chih Lee ◽  
Kai-Fu Chang ◽  
Xiao-Fan Huang ◽  
Yi-Ting Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Apoptosis ◽  
Cycle Arrest ◽  
Anticancer Effects ◽  
Pogostemon Cablin ◽  
Colorectal Cancer Cells ◽  
Potential Applicability ◽  
Cancer Suppression

Pogostemon cablin (PCa), an herb used in traditional Chinese medicine, is routinely used in the amelioration of different types of gastrointestinal discomfort. However, the mechanisms underlying the cancer suppression activity of PCa in colorectal cancer (CRC) cells have yet to be clarified. The aim of this study was to investigate the anticancer effects of PCa, specifically the induction of apoptosis in CRC cells. The growth inhibition curve of CRC cells following exposure to PCa was detected by an MTT assay. Moreover, PCa combined with 5-FU revealed a synergic effect of decreased cell viability. PCa inhibited cell proliferation and induced cell cycle arrest at the G0/G1 phase and cell apoptosis through regulation of associated protein expression. An in vivo study showed that PCa suppressed the growth of CRC via induction of cell apoptosis with no significant change in body weight or organ histology. Our results demonstrated that PCa inhibits the growth of CRC cells and induces apoptosis in vitro and in vivo, which suggests the potential applicability of PCa as an anticancer agent.

scholarly journals Butyrate suppresses motility of colorectal cancer cells via deactivating Akt/ERK signaling in histone deacetylase dependent manner

2017 ◽  
Vol 135 (4) ◽  
pp. 148-155 ◽  
Author(s):  
Qingran Li ◽  
Chujie Ding ◽  
Tuo Meng ◽  
Wenjie Lu ◽  
Wenyue Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Histone Deacetylase ◽  
Erk Signaling ◽  
Dependent Manner ◽  
Colorectal Cancer Cells

scholarly journals Verbascoside: Identification, Quantification, and Potential Sensitization of Colorectal Cancer Cells to 5-FU by Targeting PI3K/AKT Pathway

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Yasmeen M. Attia ◽  
Dina M. El-Kersh ◽  
Hebatallah A. Wagdy ◽  
Mohamed M. Elmazar
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Akt Pathway ◽  
Colorectal Cancer Cells

scholarly journals A novel inhibitor of ADAM17 sensitizes colorectal cancer cells to 5-Fluorouracil by reversing Notch and epithelial-mesenchymal transition in vitro and in vivo

2018 ◽  
Vol 51 (5) ◽  
pp. e12480 ◽  
Author(s):  
Dan-Dan Li ◽  
Chang-Hao Zhao ◽  
Huai-Wei Ding ◽  
Qiong Wu ◽  
Tian-Shu Ren ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Colorectal Cancer Cells
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