scholarly journals Emerging Effects of Sepantronium Bromide (YM155) on MOLT-4 Cell Line Apoptosis Induction and Expression of Critical Genes Involved in Apoptotic Pathways

2019 ◽  
Vol 10 (1) ◽  
pp. 81-87
Author(s):  
Kobra Shojaei Moghadam ◽  
Majid Farshdousti Hagh ◽  
Mohammad Reza Alivand ◽  
Masoumeh Fardi ◽  
Ali Akbar Movassaghpour ◽  
...  
Keyword(s):  
Cell Line ◽  
Epithelial To Mesenchymal Transition ◽  
Target Genes ◽  
Lymphoblastic Leukemia ◽  
Annexin V ◽  
Apoptosis Induction ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Apoptotic Pathways ◽  
Sepantronium Bromide

Purpose: Sepantronium bromide (YM155) is a Survivin inhibitor which recently advanced as an anticancer agent in phase II clinical trials. Survivin belongs to IAP (inhibitor of apoptosis) gene family and is a pivotal target for treatment due to its overexpression and oncogenic function in many malignancies, including acute lymphoblastic leukemia (ALL). Although survivin is a specific target for YM155, recent reports have shown that it has many other crucial targets that regulate its anti-apoptotic effects. The aim of this study was to investigate whether YM155 could have an effect on cell death-inducing genes as well as inducing apoptosis in T-ALL MOLT4- cell line. Methods: We treated MOLT-4 cells with increasing concentrations of YM155 and then cell viability was determined using MTT (methyl thiazolyl tetrazolium) assay. Also, the rate of induction of apoptosis in MOLT-4 cells and the target genes expression levels were evaluated by Annexin V/PI and real-time PCR, respectively. Results: YM155 inhibited cell growth in MOLT-4 cells. This outcome is achieved by inducing apoptosis and a significant increase in the expression level of P53, MiR-9, caspase 3 and decreasing the mRNA expression levels of survivin, Sirtuin1(SIRT1), member of anti-apoptotic proteins family (Bcl-2), and epithelial-to-mesenchymal transition (EMT) initiating factors Snail1and Zeb2. Conclusion: The results showed that use of YM155 can be a potential drug therapy in T-ALL patients with promising effects on apoptosis induction.

scholarly journals Anti-Cancer Effects of Glaucarubinone in the Hepatocellular Carcinoma Cell Line Huh7 via Regulation of the Epithelial-To-Mesenchymal Transition-Associated Transcription Factor Twist1

2021 ◽  
Vol 22 (4) ◽  
pp. 1700
Author(s):  
Jihye Seo ◽  
Jain Ha ◽  
Eunjeong Kang ◽  
Haelim Yoon ◽  
Sewoong Lee ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Wound Healing ◽  
Transcription Factor ◽  
Cell Migration ◽  
Cell Line ◽  
Intracellular Signaling ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Huh7 Cells ◽  
Anti Cancer

Hepatocellular carcinoma (HCC), the most common type of liver cancer, is a leading cause of cancer-related deaths. As HCC has a high mortality rate and its incidence is increasing worldwide, understanding and treating HCC are crucial for resolving major public health concerns. In the present study, wound healing screening assays were performed using natural product libraries to identify natural chemicals that can inhibit cancer cell migration. Glaucarubinone (GCB) showed a high potential for inhibiting cell migration. The anti-cancer effects of GCB were evaluated using the HCC cell line, Huh7. GCB showed anti-cancer effects, as verified by wound healing, cell migration, invasion, colony formation, and three-dimensional spheroid invasion assays. In addition, cells treated with GCB showed suppressed matrix metalloproteinase activities. Immunoblotting analyses of intracellular signaling pathways revealed that GCB regulated the levels of Twist1, a crucial transcription factor associated with epithelial-to-mesenchymal transition, and mitogen-activated protein kinase. The invasive ability of cancer cells was found to be decreased by the regulation of Twist1 protein levels. Furthermore, GCB downregulated phosphorylation of extracellular signal-regulated kinase. These results indicate that GCB exhibits anti-metastatic properties in Huh7 cells, suggesting that it could be used to treat HCC.

scholarly journals FH535 Potentiation of Cigarette Smoke Condensate Cytotoxicity is Associated With Changes in β-Catenin and EGR-1 Signaling

2012 ◽  
Vol 31 (4) ◽  
pp. 380-389 ◽  
Author(s):  
William W. Polk
Keyword(s):  
Cigarette Smoke ◽  
Epithelial To Mesenchymal Transition ◽  
Target Genes ◽  
Protein Localization ◽  
Bronchial Epithelial Cell ◽  
Nuclear Accumulation ◽  
Epithelial Cell Line ◽  
Cigarette Smoke Condensate ◽  
Bronchial Epithelial ◽  
Mesenchymal Transition

Cigarette smoke condensate (CSC) has been reported to elicit morphological and transcriptional changes that suggest epithelial-to-mesenchymal transition (EMT) in cultured bronchial epithelial cells. The transdifferentiation potential of acute and prolonged CSC exposure alone or in combination with the β-catenin inhibitor, FH535, was investigated in the bronchial epithelial cell line, BEAS-2B, through assessment of cell morphology, transcript expression, protein expression, and protein localization. Changes in morphology, β-catenin translocation, E-cadherin expression, metalloproteinase expression, and fibronectin could be demonstrated independent of molecular or physiological evidence of EMT. FH535 was shown to increase CSC-induced cytotoxicity and depress β-catenin expression. However, FH535 effects were not limited to the β-catenin pathway as it also blocked the expression of early growth responsive protein 1 (EGR-1) target genes, fibronectin and phosphatase and tensin homologue, without affecting EGR-1 nuclear accumulation.

scholarly journals GCC2 is a New Biomarker for Diagnosis of Early Non-Small Cell Lung Cancer and A Potential Target to Reverse Epithelial to Mesenchymal Transition

2020 ◽  
Author(s):  
Hyesun Jeong ◽  
Byeong Hyeon Choi ◽  
Jik-han Jung ◽  
Hyunku Shin ◽  
JinA Park ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Treatment ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Epithelial To Mesenchymal Transition ◽  
Small Cell ◽  
Nsclc Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition ◽  
Expression Levels

Abstract Background: Nano-sized exosomes (30–150 nm) are cell membrane-encapsulated vesicles that contain nucleic acids and proteins. Specific markers detecting non-small cell lung cancer (NSCLC) cell-derived exosomes in the blood circulation remain unidentified. Here, we report a new biomarker distinguishing cancer from non-cancer exosomes that also involved in epithelial to mesenchymal transition for cancer treatment.Methods: Exosomes were isolated from plasma of patients with various pathological stages of NSCLC and NSCLC cell lines, human pulmonary alveolar epithelial cells by size exclusion chromatography and characterized by Nanoparticle Tracking Analysis and western-blotting. The exosomes were lysed and applied to proteomic analysis. The expression levels of the GCC2 proteins from NSCLC patients were analyzed by ELISA assays, and the effects by GCC2 shRNA were analyzed by real-time RT-PCR, cell migration and colony formation assays.Results: A protein GRIP and coiled-coil domain-containing 2 (GCC2), which is involved in endosome-to-Golgi transport, was identified by the proteomics analysis of exosomes isolated from NSCLC cell lines. The GCC2 protein expression levels were increased in the exosomes derived from patients with early-stage NSCLC compared with healthy controls. The receiver operating characteristic curve of exosomal GCC2 revealed 94.74% sensitivity and 75.00% specificity, and AUC of 0.875. GCC2 knockdown experiments by GCC2 shRNA showed reduced exosome secretion in cancer cell lines, which altered the molecular and cellular properties, such as the expression levels of mesenchymal-to-epithelial genes, and cellular growth and motility.Conclusion: GCC2 represents a promising biomarker for early diagnosis of NSCLC and a therapeutic target for future cancer treatment.

scholarly journals DNA Methylation of TGFβ Target Genes: Epigenetic Control of TGFβ Functional Duality in Liver Cancer

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2207
Author(s):  
Kevin Bévant ◽  
Matthis Desoteux ◽  
Abdel Hady A. Abdel Wahab ◽  
Sabrin A. Abdel Wahab ◽  
Ayman Mohamed Metwally ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Tumor Progression ◽  
Transforming Growth Factor Beta ◽  
Epithelial To Mesenchymal Transition ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Early Stage ◽  
Potent Inducer ◽  
Mesenchymal Transition ◽  
Epigenetic Control

Transforming growth factor beta (TGFβ) plays a key role in liver carcinogenesis. However, its action is complex, since TGFβ exhibits tumor-suppressive or oncogenic properties, depending on the tumor stage. At an early stage TGFβ exhibits cytostatic features, but at a later stage it promotes cell growth and metastasis, as a potent inducer of epithelial to mesenchymal transition (EMT). Here, we evaluated DNA methylation as a possible molecular mechanism switching TGFβ activity toward tumor progression in hepatocellular carcinoma (HCC). We report that decitabine, a demethylating agent already used in the clinic for the treatment of several cancers, greatly impairs the transcriptional response of SNU449 HCC cells to TGFβ. Importantly, decitabine was shown to induce the expression of EMT-related transcription factors (e.g., SNAI1/2, ZEB1/2). We also report that the promoter of SNAI1 was hypomethylated in poor-prognosis human HCC, i.e., associated with high grade, high AFP level, metastasis and recurrence. Altogether, the data highlight an epigenetic control of several effectors of the TGFβ pathway in human HCC possibly involved in switching its action toward EMT and tumor progression. Thus, we conclude that epidrugs should be carefully evaluated for the treatment of HCC, as they may activate tumor promoting pathways.

scholarly journals Reversal of glucocorticoid resistance in Acute Lymphoblastic Leukemia cells by miR-145

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9337
Author(s):  
Sili Long ◽  
Danwei Ren ◽  
Fangfang Zhong ◽  
Yana Niu ◽  
Xiang Qin ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Line ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cells ◽  
Expression Levels ◽  
Disease Prognosis ◽  
Cell Proliferation Inhibition ◽  
Apoptotic Genes ◽  
Target Database ◽  
Geo Database

Objective To analyze the expression levels of miR-145 in ALL children and their effects on the prognosis of ALL and to explore the mechanism of miR-145 in reversing the resistance of ALL cells to glucocorticoids. Methods A GEO database dataset was used to analyze the expression levels of miR-145 in ALL children. The association between miR-145 and childhood prognosis was analyzed by the TARGET database data. The expression levels of miR-145 in the glucocorticoid-resistant ALL cell line CEM-C1 were increased by lipofectamine 2000-mediated transfection. Cell proliferation inhibition experiments were performed to detect the effect of miR-145 on the response of CEM-C1 cell line to glucocorticoids. The expression levels of the apoptotic, autophagic and drug resistance-associated genes and proteins were detected by qPCR and western blot analysis. Results The expression levels of miR-145 were decreased in ALL patients (P < 0.001) and the prognosis of ALL in children with high miR-145 expression was significantly improved (P < 0.001). Increased miR-145 expression can improve the sensitivity of CEM-C1 cells to glucocorticoids. The expression levels of the proapoptotic and the anti-apoptotic genes Bax and Bcl-2 were increased and decreased, respectively, whereas the expression levels of the autophagicgenes Beclin 1 and LC were increased. In addition, the expression levels of the drug resistance gene MDR1 were decreased. Conclusion The expression levels of miR-145 in ALL children were decreased and they were associated with disease prognosis. The data indicated that miR-145 can reverse cell resistance by regulating apoptosis of CEM-C1 cells and autophagy.

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