scholarly journals Baicalein Inhibits Metastatic Phenotypes in Nasopharyngeal Carcinoma Cells via a Focal Adhesion Protein Integrin β8

2021 ◽  
Vol 15 (1) ◽  
pp. 5
Author(s):  
Pichamon Kiatwuthinon ◽  
Thana Narkthong ◽  
Utapin Ngaokrajang ◽  
Supeecha Kumkate ◽  
Tavan Janvilisri
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Cell Lines ◽  
Focal Adhesion ◽  
Biological Effects ◽  
Transcriptome Profiling ◽  
Anticancer Activities ◽  
Scutellaria Baicalensis Georgi ◽  
Study Results ◽  
Underlying Mechanisms ◽  
Focal Adhesion Pathway

Baicalein, a prominent flavonoid from the indigenous herbal plant Scutellaria baicalensis Georgi, possesses broad-spectrum anticancer activities. However, the biological effects of baicalein on nasopharyngeal carcinoma (NPC) and its underlying mechanisms remain unclarified. Thus, in this study, we examined the effects of baicalein on NPC cell lines and investigated the corresponding molecular mechanism through transcriptome profiling. In the study, four NPC cell lines were treated with various concentrations of baicalein at different time points. Cellular toxicity and proliferative inhibition of baicalein were examined by MTT assay. Metastatic phenotypes of NPC cells were investigated by wound healing, transwell, and adhesion assays. Additionally, microarray experiments were performed to determine the cellular pathways affected by baicalein. The expression and localization of the integrin β8 were validated by western immunoblotting and immunofluorescence. Our results revealed that baicalein exhibited its cytotoxicity and antiproliferative activity on all tested NPC cell lines. It also significantly inhibited metastatic phenotypes at sub-lethal concentrations. Transcriptomic analysis showed that baicalein significantly affected the focal adhesion pathway in NPC, where integrin β8 was greatly diminished. Thus, the present study results suggested that baicalein inhibits the metastatic phenotypes of NPC cells by modulating integrin β8, one of the major molecules in a focal adhesion pathway.

scholarly journals N1, N12-Diacetylspermine Is Elevated in Colorectal Cancer and Promotes Proliferation through the miR-559/CBS Axis in Cancer Cell Lines

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Teng Mu ◽  
Tingguang Chu ◽  
Wenxin Li ◽  
Qianze Dong ◽  
Yong Liu
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Cell Cycle Progression ◽  
Polyclonal Antibodies ◽  
Biological Effects ◽  
Clinical Stage ◽  
Luciferase Reporter ◽  
E Proteins ◽  
Atp Production ◽  
Underlying Mechanisms

N1, N12-Diacetylspermine (DiAcSpm) has been reported to be upregulated in the urine of cancer patients. Mass spectrometry has shown elevated DiAcSpm expressions in colorectal cancer (CRC) tissues. However, the diagnostic application of DiAcSpm is not available due to a lack of diagnostic grade antibodies. Also, its biological roles in CRC cells remain unexplored. In the present study, we developed an antibody that directly detected DiAcSpm expression in paraffin-embedded tissues. We also characterized its biological characteristics and underlying mechanisms. Polyclonal antibodies were generated by immunizing animals with a synthetic product of DiAcSpm. Antibody DAS AB016 showed strong sensitivity against DiAcSpm in CRC tissues. Immunohistochemistry results showed that DiAcSpm expression was significantly elevated in CRC tissues. High levels of DiAcSpm correlated with the clinical stage and Ki67 index. DiAcSpm treatment increased levels of proliferation, cell cycle progression, and cyclin D1 and cyclin E proteins in CRC cell lines, SW480 and Caco-2. DiAcSpm also upregulated ATP production in these two cell lines. RNA-sequencing showed that DiAcSpm downregulated miR-559, which was confirmed using RT-qPCR. The luciferase reporter assay, western blotting, and RT-qPCR showed that cystathionine β-synthase (CBS) was the target of miR-559. miR-559 inhibited, while CBS accelerated, CRC proliferation. In addition, CBS siRNA knockdown blocked the biological effects of DiAcSpm on CRC cells. In conclusion, DiAcSpm was found to be increased in CRC tissues using a newly developed antibody. DiAcSpm accelerated CRC proliferation by regulating the miR-559/CBS axis.

Underlying mechanisms for LTF inactivation and its functional analysis in nasopharyngeal carcinoma cell lines

2011 ◽  
Vol 112 (7) ◽  
pp. 1832-1843 ◽  
Author(s):  
Hejun Zhang ◽  
Xiangling Feng ◽  
Weidong Liu ◽  
Xingjun Jiang ◽  
Wenjiao Shan ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Nasopharyngeal Carcinoma ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
Nasopharyngeal Carcinoma Cell ◽  
Carcinoma Cell Lines ◽  
Underlying Mechanisms

scholarly journals PPAR-γ Ligand Inhibits Nasopharyngeal Carcinoma Cell Proliferation and Metastasis by Regulating E2F2

PPAR Research ◽  
2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Ping-Li Yang ◽  
Jia-Shun Wang ◽  
Xiao-Mei Cheng ◽  
Jing-Cai Chen ◽  
Hui Zhu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Nasopharyngeal Carcinoma ◽  
Cell Lines ◽  
Cellular Proliferation ◽  
Nuclear Hormone Receptor ◽  
Advanced Tumor Stage ◽  
Study Results ◽  
Proliferation And Metastasis ◽  
Cell Proliferation And Metastasis

Purpose. Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a nuclear hormone receptor with a key role in lipid metabolism. Previous studies have identified various roles of PPAR-γ in cell cycle progression, cellular proliferation, and tumor progression. However, no report has described a role for PPAR-γ in human nasopharyngeal carcinoma (NPC). Notably, some studies have reported a relationship between PPAR-γ and E2F transcription factor 2 (E2F2), which has been identified as a regulator of cell cycle, apoptosis, and the DNA damage response. Notably, E2F2 has also been reported to correlate with a poor prognosis in patients with various malignancies. Methods. We used immunohistochemical (IHC) and western blot methods to evaluate PPAR-γ and E2F2 expression and function in nonkeratinizing NPC and nasopharyngitis (NPG) tissue samples, as well as western blotting and CCK8 analyses in the NPC cell lines, CNE1 and CNE2. Results. We observed lower levels of PPAR-γ expression in nonkeratinizing NPC tissues compared with NPG tissues and determined an association between a low level of PPAR-γ expression with a more advanced tumor stage. Furthermore, strong E2F2 expression was detected in nonkeratinizing NPC tissues. We further demonstrated that rosiglitazone, a PPAR-γ agonist, reduced E2F2 expression and proliferation in NPC cell lines. Conclusions. Our study results revealed a novel role for the PPAR-γ–E2F2 pathway in controlling NPC cell proliferation and metastasis.

scholarly journals Casticin inhibits nasopharyngeal carcinoma growth by targeting phosphoinositide 3-kinase

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jingxian Liu ◽  
Jinghong Yang ◽  
Yuhe Hou ◽  
Zhenwei Zhu ◽  
Jie He ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Nasopharyngeal Carcinoma ◽  
Cell Lines ◽  
Three Dimensional ◽  
Annexin V ◽  
Pi3k Inhibitor ◽  
Anticancer Activities ◽  
Pharmacological Agents ◽  
Phosphoinositide 3 Kinase

Abstract Background Casticin, an isoflavone compound extracted from the herb Fructus Viticis, has demonstrated anti-inflammatory and anticancer activities and properties. The aim of this study was to investigate the effects and mechanisms of casticin in nasopharyngeal carcinoma (NPC) cells and to determine its potential for targeted use as a medicine. Methods NPC cells were used to perform the experiments. The CCK‑8 assay and colony formation assays were used to assess cell viability. Flow cytometry was used to measure the cell cycle and apoptosis analysis (annexin V/PI assay). A three-dimensional (3D) tumour sphere culture system was used to characterize the effect of casticin on NPC stem cells. In silico molecular docking prediction and high-throughput KINOME scan assays were used to evaluate the binding of casticin to phosphoinositide 3-kinase (PI3K), including wild-type and most of mutants variants. We also used the SelectScreen assay to detect the IC50 of ATP activity in the active site of the target kinase. Western blotting was used to evaluate the changes in key proteins involved cell cycle, apoptosis, stemness, and PI3K/protein kinase B (AKT) signalling. The effect of casticin treatment in vivo was determined by using a xenograft mouse model. Results Our results indicate that casticin is a new and novel selective PI3K inhibitor that can significantly inhibit NPC proliferation and that it induces G2/GM arrest and apoptosis by upregulating Bax/BCL2 expression. Moreover, casticin was observed to affect the self-renewal ability of the nasopharyngeal carcinoma cell lines, and a combination of casticin with BYL719 was observed to induce a decrease in the level of the phosphorylation of mTORC1 downstream targets in BYL719-insensitive NPC cell lines. Conclusion Casticin is a newly emerging selective PI3K inhibitor with potential for use as a targeted therapeutic treatment for nasopharyngeal carcinoma. Accordingly, casticin might represent a novel and effective agent against NPC and likely has high potential for combined use with pharmacological agents targeting PI3K/AKT.

DNA Methylation Inhibites ANXA1 Gene Expression in Nasopharyngeal Carcinoma Cell Lines*

2009 ◽  
Vol 36 (10) ◽  
pp. 1319-1326 ◽  
Author(s):  
Shuang-Xiang TAN ◽  
Rui-Cheng HU ◽  
Ai-Guo DAI ◽  
Cen-E TANG ◽  
Hong YI ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Nasopharyngeal Carcinoma ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
Nasopharyngeal Carcinoma Cell ◽  
Carcinoma Cell Lines

Syntheses and Cytotoxicity Screening of some Novel 1,2,4-Triazine Derivatives against Liver Carcinoma Cell Lines

2020 ◽  
Vol 17 ◽  
Author(s):  
W. Abd El-Fattah
Keyword(s):  
Acetic Anhydride ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
Aromatic Aldehydes ◽  
Liver Carcinoma ◽  
Anticancer Activities ◽  
Carcinoma Cell Lines ◽  
Elemental Analyses ◽  
Triazine Derivatives ◽  
C Nmr

: In this work, 1,2,4-triazine derivatives were synthesized and evaluated for anticancer activities. Series of 1,2,4-triazine derivatives (4a, b) were prepared via the reaction of N-benzoyl glycine (1) with aromatic aldehydes in presence of fused sodium acetate and acetic anhydride to give 1,3-oxazolinone derivatives (2a, b), followed by condensation with 1-(ethoxycarbonyl) hydrazine (3) in glacial acetic acid. Compounds (4a, b) then reacted with acetic anhydride, ethyl chloroacetate and 2,4-dinitrophenyl hydrazine yielded the corresponding to N-acetyl derivatives (5a, b), N-(ethoxycarbonyl) methyl derivative (6) and 1,2-disubstituted hydrazine (7), respectively. The structures of the 1,2,4-triazine derivatives were confirmed by IR, 1H, 13C NMR, MS and elemental analyses. Anticancer activity of some 1,2,4-triazine derivatives (4-7) have been investigated. The results revealed that compounds 4a (IC50= 2.7μM), 5a (IC50= 1.5μM), and 5b (IC50= 3.9μM) show promising inhibitory growth efficacy compared to a standard antitumor drug (IC50= 4.6μM). These three compounds can be considered as potential agents against human hepatocellular carcinoma cell lines (HepG-2).

Anticancer Activity and Topoisomerase II Inhibition of Naphthalimides with ω-Hydroxylalkylamine Side-Chains of Different Lengths

2019 ◽  
Vol 15 (5) ◽  
pp. 550-560
Author(s):  
Mateusz D. Tomczyk ◽  
Anna Byczek-Wyrostek ◽  
Klaudia Strama ◽  
Martyna Wawszków ◽  
Przemysław Kasprzycki ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Cell Lines ◽  
Inhibitory Activity ◽  
Topoisomerase Ii ◽  
Significant Activity ◽  
Anticancer Activities ◽  
Human Colon Cancer ◽  
Substitution Pattern ◽  
Topo Ii

Background: The substituted 1,8-Naphthalimides (1H-benzo[de]isoquinoline-1,3(2H)- diones) are known as DNA intercalators stabilizing DNA-Topoisomerase II complexes. This interaction disrupts the cleavage-relegation equilibrium of Topo II, resulting in formation of broken strands of DNA. Objective: To investigate the influence of type of substituents and substitution positions in 1,8- naphthalimde skeleton on the inhibition of Topoisomerase II activity. Methods: The starting 1,8-naphthalimide were prepared from acenaphthene by introduction of appropriate substituents followed by condensation with ω-hydroxylakylamines of different chain length. The substituents were introduced to 1,8-naphthalimide molecule by nucleophilic substitution of leaving groups like nitro or bromo present in 4 or 4,5- positions using the ω- hydroxylalkylamines. The bioactivity of obtained compounds was examined in model cell lines. Results: Antiproliferative activity of selected compounds against HCT 116 human colon cancer cells, human non-small cell lung cells A549 and non-tumorigenic BEAS-2B human bronchial epithelium cells was examined. Several of investigated compounds exhibit a significant activity (IC50 µM to 7 µM) against model cancer cell lines. It was demonstrated that upon treatment with concentration of 200 µM, all derivatives display Topo II inhibitory activity, which may be compared with activity of Amonafide. Conclusion: The replacement of the nitro groups in the chromophore slightly reduces its anticancer activities, whereas the presence of both nitro group and ω-hydroxylalkylamine chain resulted in seriously increased anticancer activity. Obtained compounds showed Topo II inhibitory activity, moreover, influence of the substitution pattern on the ability to inhibit Topo II activity and cancer cells proliferation was observed.

New Spirocyclic Hydroxamic Acids as Effective Antiproliferative Agents

2020 ◽  
Vol 20 ◽  
Author(s):  
Margarita E. Neganova ◽  
Sergey G. Klochkov ◽  
Yulia R. Aleksandrova ◽  
Vladimir N. Osipov ◽  
Dmitry V. Avdeev ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Histone Deacetylase ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Antioxidant Activities ◽  
Hydroxamic Acids ◽  
Cytotoxic Activities ◽  
Tumor Cell Lines ◽  
Hek 293 ◽  
Underlying Mechanisms

Aims: The main goal of this work where is to synthesize new original spirocyclic hydroxamic acids, investigate their cytotoxicity against to the panel of tumor cell lines and possible mechanism of action of these active compounds. Background: Hydroxamic acids are one of the promising classes of chemical compounds with proven has anticancer potential properties. This is manifested in the presence of metal chelating and antioxidant activities, the ability to inhibit histone deacetylase enzymes and a chemosensitizing effect against well known cytostatics. Objective: Original spirocyclic hydroxamic acids were synthesized and spectrums of their antiproliferative activities were investigated. Methods: The cytotoxic activities on different tumor lines (SH-SY5Y, HeLa and healthy cells HEK-293) were investigated and determined possible underlying mechanisms of their activity. Result: New original spirocyclic hydroxamic acids were synthesized. These compounds exhibit antiproliferative properties against of the various tumor cultures cells and also exhibits antioxidant activity, a depolarizing effect on the mitochondrial membrane, inhibit the activity of the histone deacetylase enzyme, and also decrease of basal glycolysis and glycolytic capacity reserve of HeLa and SH-SY5Y tumor cell lines. Conclusion: The most promising are compounds 5j-l containing two chlorine atoms as substituents in the quinazoline part of the molecule and hydroxamate function. Therefore, these compounds can be considered as hit compounds for the development on their basis multi-target anticancer agents.

Design, Synthesis, In Vitro Anti-cancer Activity, ADMET Profile and Molecular Docking of Novel Triazolo[3,4-a]phthalazine Derivatives Targeting VEGFR-2 Enzyme

2018 ◽  
Vol 18 (8) ◽  
pp. 1184-1196 ◽  
Author(s):  
Abdel-Ghany A. El-Helby ◽  
Helmy Sakr ◽  
Rezk R.A. Ayyad ◽  
Khaled El-Adl ◽  
Mamdouh M. Ali ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Docking ◽  
Cell Lines ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Kinase Assay ◽  
Anticancer Activities ◽  
In Silico Admet ◽  
Human Colon Adenocarcinoma ◽  
Mcf 7

Background: Extensive studies were reported in the synthesis of several phthalazine derivatives as promising anticancer agents as potent VEGFR-2 inhibitors. Vatalanib (PTK787) was the first anilinophthalazine published derivative as a potent inhibitor of VEGFR. The discovery of vatalanib as a clinical candidate led to the design and synthesis of different anilinophthalazine derivatives as potent inhibitors for VEGFR-2. The objective of present research work is the synthesis of new agents with the same essential pharmacophoric features of the reported and clinically used VEGFR-2 inhibitors (e.g vatalanib and sorafenib). The main core of our molecular design rationale comprised bioisosteric modification strategies of VEGFR-2 inhibitors at four different positions. </P><P> Material and Methods: A correlation between structure and biological activity of our designed phthalazines was established using molecular docking and VEGFR-2 kinase assay. Results and Discussion: In view of their expected anticancer activity, novel triazolo[3,4-a]phthalazine derivatives 5-6a-o and 3-substituted-bis([1,2,4]triazolo)[3,4-a:4',3'-c]phthalazines 9a-b were designed, synthesized and evaluated for their anti-proliferative activity against two human tumor cell lines HCT-116 human colon adenocarcinoma and MCF-7 breast cancer. It was found that, compound 6o the most potent derivative against both HCT116 and MCF-7 cancer cell lines. Compounds 6o, 6m, 6d and 9b showed the highest anticancer activities against HCT116 human colon adenocarcinoma with IC50 of 7±0.06, 13±0.11, 15±0.14 and 23±0.22 µM respectively while compounds 6o, 6d, 6a and 6n showed the highest anticancer activities against MCF-7 breast cancer with IC50 of 16.98±0.15, 18.2±0.17, 57.54±0.53 and 66.45±0.67 µM respectively. Sorafenib as a highly potent VEGFR-2 inhibitor was used as a reference drug with IC50 of 5.47±0.3 and 7.26±0.3 µM respectively. Nine compounds were further evaluated for their VEGFR-2 inhibitory activity. Compounds 6o, 6m, 6d and 9b emerged as the most active counterparts against VEGFR-2 with IC50 values of 0.1±0.01, 0.15±0.02, 0.28±0.03 and 0.38±0.04 µM, respectively comparable to that of sorafenib (IC50 = 0.1±0.02) µM. Furthermore, molecular docking studies were carried out for all synthesized compounds to investigate their binding pattern and predict their binding affinities towards VEGFR-2 active site. In silico ADMET studies were calculated for the tested compounds. Most of our designed compounds exhibited good ADMET profile. Conclusion: The obtained results showed that, the most active compounds could be useful as a template for future design, optimization, adaptation and investigation to produce more potent and selective VEGFR-2 inhibitors with higher anticancer analogs.

MiR-597 Targeting 14-3-3σ Enhances Cellular Invasion and EMT in Nasopharyngeal Carcinoma Cells

2019 ◽  
Vol 12 (2) ◽  
pp. 105-114 ◽  
Author(s):  
Lisha Xie ◽  
Tao Jiang ◽  
Ailan Cheng ◽  
Ting Zhang ◽  
Pin Huang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Cell Lines ◽  
Western Blotting ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Suppressor Gene ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Downstream Target ◽  
Before And After

Background: Alterations in microRNAs (miRNAs) are related to the occurrence of nasopharyngeal carcinoma (NPC) and play an important role in the molecular mechanism of NPC. Our previous studies show low expression of 14-3-3σ (SFN) is related to the metastasis and differentiation of NPC, but the underlying molecular mechanisms remain unclear. Methods: Through bioinformatics analysis, we find miR-597 is the preferred target miRNA of 14-3-3σ. The expression level of 14-3-3σ in NPC cell lines was detected by Western blotting. The expression of miR-597 in NPC cell lines was detected by qRT-PCR. We transfected miR-597 mimic, miR-597 inhibitor and 14-3-3σ siRNA into 6-10B cells and then verified the expression of 14-3-3σ and EMT related proteins, including E-cadherin, N-cadherin and Vimentin by western blotting. The changes of migration and invasion ability of NPC cell lines before and after transfected were determined by wound healing assay and Transwell assay. Results: miR-597 expression was upregulated in NPC cell lines and repaired in related NPC cell lines, which exhibit a potent tumor-forming effect. After inhibiting the miR-597 expression, its effect on NPC cell line was obviously decreased. Moreover, 14-3-3σ acts as a tumor suppressor gene and its expression in NPC cell lines is negatively correlated with miR-597. Here 14-3-3σ was identified as a downstream target gene of miR-597, and its downregulation by miR-597 drives epithelial-mesenchymal transition (EMT) and promotes the migration and invasion of NPC. Conclusion: Based on these findings, our study will provide theoretical and experimental evidences for molecular targeted therapy of NPC.

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