scholarly journals Liposomal Curcumin Targeting Endometrial Cancer Through the NF-κB Pathway

2018 ◽  
Vol 48 (2) ◽  
pp. 569-582 ◽  
Author(s):  
Hanzi Xu ◽  
Zhen Gong ◽  
Siying Zhou ◽  
Sujin Yang ◽  
Dandan Wang ◽  
...  
Keyword(s):  
Cell Motility ◽  
Tumor Model ◽  
Pcr Analysis ◽  
Therapeutic Effects ◽  
Zebrafish Model ◽  
Inhibition Of Proliferation ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition

Background/Aims: Emerging evidence suggests that curcumin possesses chemopreventive properties against various cancers. However, its poor bioavailability limits its clinical application. In this study, we aimed to utilize encapsulation in liposomes (Lipo) as a strategy for the clinical administration of curcumin for endometrial carcinoma (EC). Methods: Curcumin was encapsulated in a liposomal delivery system to prepare a formulation of liposomal curcumin (LC). EC cell lines Ishikawa and HEC-1 were treated with the compound and cell proliferation was measured using MTT assay. Hoechst 33258 staining assay and flow cytometry were used to detect apoptosis of the cells. Wound healing and cell invasion assays were employed to monitor cell motility. Underlying target signaling, such as NF-κB, caspases, and MMPs, were further studied via qRT-PCR and western blot. Thereafter, a zebrafish model was used to assess the toxicity of LC. Finally, a zebrafish transplantation tumor model of EC was grown and treated with LC. Tumors were monitored and harvested to study the expression of NF-κB. Results: The formation of LC was successfully developed with excellent purity and physical properties. In vitro, LC resulted in dose-dependent inhibition of proliferation, induction of apoptosis, and suppression of Ishikawa and HEC-1 cell motility. LC treatment also suppressed the activation and/or expression of NF-κB, caspase-3, and MMP-9. No demonstrable toxicity was found in the zebrafish model and tumors were suppressed after treatment with LC. PCR analysis also showed down-regulated expression of NF-κB. Conclusions: LC was successfully prepared and played biological roles against EC probably through negative regulation of the NF-κB pathway in vitro and in vivo, which demonstrates its potential therapeutic effects in EC.

scholarly journals lncRNA MEG3 Suppresses the Tumorigenesis of Hemangioma by Sponging miR-494 and Regulating PTEN/ PI3K/AKT Pathway

2018 ◽  
Vol 51 (6) ◽  
pp. 2872-2886 ◽  
Author(s):  
Yuxin Dai ◽  
Yongkun Wan ◽  
Mingke Qiu ◽  
Shuqing Wang ◽  
Chang Pan ◽  
...  
Keyword(s):  
Negative Correlation ◽  
Colony Formation ◽  
Normal Skin ◽  
Ectopic Expression ◽  
Tumor Model ◽  
Bioinformatic Analysis ◽  
Akt Pathway ◽  
Pcr Analysis

Background/Aims: Dysregulation of long noncoding RNAs (lncRNAs) is associated with the proliferation and metastasis in a variety of cancers, of which lncRNA maternally expressed gene 3 (MEG3) has been indicated as a tumor suppressor in multiple malignancies. However, the underlying mechanisms by which MEG3 contributes to human hemangiomas (HAs) remain undetermined. Methods: qRT-PCR analysis was performed to examine the expression levels of MEG3 and VEGF in proliferating or involuting phase HAs. MTT, colony formation assay, flow cytometry analysis and a subcutaneous xenograft tumor model were conducted to assess the effects of MEG3 on the HAs tumorigenesis. The interaction between MEG3 and miRNAs or their downstream pathways was evidenced by bioinformatic analysis, luciferase report assays, RNA immunoprecipitation (RIP) assay. and Western blot analysis. Results: The expression of MEG3 was substantially decreased and had a negative correlation with VEGF expression in proliferating phase HAs, as compared with the involuting phase HAs and normal skin tissues. Ectopic expression of MEG3 suppressed cell proliferation, colony formation and induced cycle arrest in vitro and in vivo, followed by the downregulation of VEGF and cyclinD1, but knockdown of MEG3 reversed these effects. Furthermore, MEG3 was verified to act as a sponge of miR-494 in HAs cells, and miR-494 counteracted MEG3-caused anti-proliferative effects by regulating PTEN/PI3K/AKT pathway, and exhibited the negative correlation with MEG3 and PTEN expression in proliferating phase HAs. Conclusion: Our findings suggested that lncRNA MEG3 inhibited HAs tumorigenesis by sponging miR-494 and regulating PTEN/PI3K/AKT pathway.

scholarly journals Circular RNA_CNST Promotes the Tumorigenesis of Osteosarcoma Cells by Sponging miR-421

2020 ◽  
Vol 29 ◽  
pp. 096368972092614
Author(s):  
Ji-Hai Wang ◽  
Xue-Jian Wu ◽  
Yong-Zhuang Duan ◽  
Feng Li
Keyword(s):  
Colony Formation ◽  
Specific Binding ◽  
Tumor Model ◽  
Gene Expression Omnibus ◽  
Pcr Analysis ◽  
Circular Rnas ◽  
Xenograft Tumor ◽  
Potential Biomarker

Circular RNAs (circRNAs) act crucial roles in the progression of multiple malignancies including osteosarcoma (OS). But, the underlying mechanisms by which hsa_circ_0017311 (circCNST) contributes to the tumorigenesis of OS remain poorly understood. Our present study aimed to explore the role and mechanisms of circCNST in OS tumorigenesis. The differentially expressed circRNAs were identified by the Gene Expression Omnibus database. The association of circCNST with clinicopathological features and prognosis in patients with OS was analyzed by RNA fluorescence in situ hybridization (FISH) and quantitative real-time polymerase chain reaction (PCR) analysis. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation assays, and a xenograft tumor model were conducted to assess the role of circCNST in OS cells in vitro and in vivo. CircCNST-specific binding with miR-421 was confirmed by FISH, luciferase gene report, and RNA immunoprecipitation assays. As a result, we found that the expression levels of circCNST were dramatically increased in OS tissues and cell lines as compared with the adjacent normal tissues, and it was associated with tumor size and poor survival in OS patients. Knockdown of circCNST repressed cell viability, colony formation, and xenograft tumor growth, while restored expression of circCNST reversed these effects. Furthermore, circCNST was colocalized with miR-421 in the cytoplasm and acted as a sponge of miR-421, which attenuated circCNST-induced proliferation-promoting effects in OS cells by targeting SLC25A3. In conclusion, our findings demonstrate that circCNST promotes the tumorigenesis of OS cells by sponging miR-421, and provides a potential biomarker for patients with OS.

scholarly journals Inhibition of duck hepatitis B virus replication by 2',3'-dideoxy-3'-fluoroguanosine in vitro and in vivo.

1996 ◽  
Vol 40 (3) ◽  
pp. 792-794 ◽  
Author(s):  
P Hafkemeyer ◽  
A Keppler-Hafkemeyer ◽  
M A al Haya ◽  
M von Janta-Lipinski ◽  
E Matthes ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Strong Inhibitor ◽  
Duck Hepatitis B Virus ◽  
Duck Hepatitis ◽  
B Virus ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition

The antiviral activity of 2',3'-dideoxy-3'-fluoroguanosine (FdG) or its triphosphate was evaluated in the duck hepatitis B virus (DHBV) system in vitro and in vivo. In primary DHBV-infected hepatocytes FdG results in a dose-dependent inhibition of viral replication with a nearly complete inhibition at a concentration of 1 microM. Also in vivo, FdG treatment of DHBV-infected ducklings reduces DHBV DNA replication by more than 90%. These data demonstrate that FdG is a strong inhibitor of DHBV replication in vitro and in vivo.

A Novel 4-anilino-3-quinolinecarbonitrile Dual Src and Abl Kinase Inhibitor (SKI-606) Has In Vitro Activity on CML Ph+Blast Cells Resistant to Imatinib.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1991-1991 ◽  
Author(s):  
Tiziana Grafone ◽  
Manuela Mancini ◽  
Emanuela Ottaviani ◽  
Matteo Renzulli ◽  
Frank Boschelli ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Kinase Inhibitor ◽  
Blast Crisis ◽  
G1 Phase ◽  
Inhibition Of Proliferation ◽  
Cd34 Cells ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

Abstract The tyrosine kinase Bcr-Abl is the fusion product of a reciprocal translocation between chromosomes 9 and 22, known as Philadelphia chromosome and it is present in the leukemic cells of more than 95% of patients with chronic myeloid leukemia (CML). Overexpression of Bcr-Abl in myeloid cells activates various signaling pathways. Previous studies have demonstrated that certain Src family kinases, such as Hck and Lyn, are also targets of Bcr-Abl activity. Hck and Lyn are expressed and activated in CML blast-crisis patients and their increased expression correlates with disease progression or STI571 resistance in some CML patients. Resistance to STI571 seems to be mediated by amplification of or mutations in the Bcr-Abl gene, reducing sensitivity to this inhibitor; newer Abl inhibitors may be susceptible to the same mechanism of resistance. Alternative strategies for control of CML, including the biological relevance of the Bcr-Abl - Src family kinase pathway, are necessary. One such strategy is the use of a specific small molecule Src kinase inhibitor. Recently, a new class of compounds, 4-anilino-3-quinolinecarbonitrile Src kinase inhibitors, has been synthesized. One member of this class, SKI606, is a dual-specificity inhibitor of both Src family and Abl kinases. To investigate the effect in vitro of SKI-606, we analyzed human cell lines from CML patients in blast crisis (K562, MK2, LAMA) and CD34+ from 9 patients in CML blast crisis using a wide range of concentrations (0.01μM-10μM) of this novel agent. Cell cycle analysis, in particular for the cell lines, showed that a major effect of SKI606 is to alter cell cycle progression, producing G1/S arrest. SKI606 induced dose-dependent inhibition of proliferation with IC50 of 1μM at 24hr. Flow cytometric analysis with Annexin-V showed that SKI-606 induced apoptosis of 50% of cells at 48hr. Western blotting and immuno-blotting analyses showed reduced phosphorylation of Bcr-Abl and also of Lyn and Hck. We also demonstrated activation of Caspase-9, an effector cysteine-protease, after exposure to SKI606. These drug effects also reduced the oncogenic effects of the Bcr-Abl gene product in CD34+ cells from patients with CML blast crisis. SKI606 induced a dose-dependent inhibition of proliferation with an IC50 of 1μM at 48hr and induction of apoptosis at 72hr. Cytofluorimetric analysis after 72hr of exposure revealed marked accumulation of cells in the G1 phase of cell cycle, accompanied by a significant increase in the number of apoptotic cells. In some of these patient samples, we observed hypophosphorylation of Bcr-Abl, Hck and Lyn at low concentration of SKI606 (1uM at 24h, 10uM at 48h). Interestingly, CD34+ cells taken from two of our imatinib-resistant patients with Bcr-Abl point mutations (E255K and Y253H) in the P-loop region of the protein exhibited a significant increase of apoptosis (50%) and a block in G1 phase of the cell cycle after treatment with 1 μM SKI606 for 48h. Our study thus showed a potential therapeutic usefulness of the drug in treatment of CML, particularly in blast crisis phase. Ongoing gene expression profiles will contribute to further understanding of the drug mechanism.

scholarly journals 1-(4-Methoxyphenyl)-3-(3-phenoxyphenyl) prop-2-en-1-one: A Diphenyl Chalcone Derivative with Potent Antitumor Activity Via Up-Regulation of p21 Gene

2021 ◽  
pp. 1-8
Author(s):  
Litty Joseph ◽  
Lakshmi PS ◽  
Litty Joseph
Keyword(s):  
Antitumor Activity ◽  
Cytotoxic Activity ◽  
Solid Tumor ◽  
Tumor Model ◽  
Pcr Analysis ◽  
Anticancer Activities ◽  
Abnormal Cells ◽  
Solid Tumor Model

Background and Aim: Cancer is a disease of complex aetiology and is characterised by uncontrolled growth of abnormal cells. It is a major worldwide health problem. Many natural and synthetic chalcone or their derivatives showed anticancer activities. The aim of the present study is to evaluate the anticancer activity of novel chalcone derivatives and also to establish possible mechanism of action. Materials and Methods: A series of chalcones 3-(3-phenoxyphenyl)-1-phenylprop-2-en-1-one (2a); 1-(4-chlorophenyl)-3-(3-phenoxyphenyl) prop-2-en-1-one (2b); 1-(4-fluorophenyl)-3-(3-phenoxyphenyl) prop-2-en-1-one (2c); 1-(4-Nitro-phenyl)-3-(3-phenoxy-phenyl)prop-2-en-1-one (2d); 1-(4-methoxyphenyl)-3-(3-phenoxyphenyl) prop-2-en-1-one(2e) were evaluated for the cytotoxic activity both in vitro and in vivo. The in vivo antitumor activity of these compounds was estimated on Daltons Ascites Lymphoma induced solid tumor model. The effect of promising compound was further analysed by flow cytometer and RT- PCR analysis. Results and Conclusion: 1-(4-methoxyphenyl)-3-(3-phenoxyphenyl) prop-2-en-1-one and 1-(4- chlorophenyl)-3-(3-phenoxyphenyl) prop-2-en-1-one was showed in vitro cytotoxic activity, DNA damage and antiproliferative activity. DLA induced solid tumor model suggested that 1-(4-methoxyphenyl)-3-(3- phenoxy phenyl) prop-2-en-1-one significantly reduced the tumor volume, increase the percentage tumor inhibition and reverse the haematological parameters. Flow cytometry analysis concluded that the compound induces cell cycle arrest at G0/G1 phase due to the over expression of p21. 1-(4-methoxyphenyl)-3-(3- phenoxy phenyl) prop-2-en-1-one may be a potential agent for cancer treatment.

scholarly journals ANTI-TUMOR EFFECT OF CPDA ENANTIOMERS IN VITRO IN THE MODEL OF ACUTE LYMPHOBLASTIC LEUKEMIA

2017 ◽  
Vol 16 (1) ◽  
pp. 61-69
Author(s):  
A. V. Savinkova ◽  
L. R. Tilova ◽  
O. I. Borisova ◽  
E. M. Zhidkova ◽  
K. A. Kuzin ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Lymphoblastic Leukemia ◽  
Biological Properties ◽  
Pcr Analysis ◽  
Therapeutic Effects ◽  
Blood Cancer ◽  
Apoptotic Effects ◽  
Anti Tumor Activity

Introduction. Glucocorticoids are the important component of combined chemotherapy of blood cancer. Therapeutic effects of glucocorticoids is realized via activation of glucocorticoid receptor transrepression, the development of side effects is associated with transactivation. We demonstrated earlier that compound belonging the class of selective glucocorticoid receptor agonists, CpdA, selectively induced transrepression in blood cancer cells. CpdA represents a mixture of two enantiomers, which can differ in interaction with the receptor. Aim. The main aim of present study was to synthesize CpdA enantiomers and to evaluate their biological properties. Materials and methods. Synthesis was carried out based on Sharpless dihydroxylation; anti-tumor activity in vitro was evaluated by antiproliferative and pro-apoptotic effects. Ligand properties were estimated by PCR-analysis of glucocorticoid- and NF-kB-dependent genes expression. Results and conclusions. We demonstrated that CpdA enantiomers revealed anti-tumor activity in vitro and did not induce transactivation. Moreover, S-enantiomer of CpdA in the most tests demonstrated more pronounced activity and is more perspective molecule for future studies in vivo.

Triazolylthioacetamides Confer Inhibitory Efficacy against Metallo-β-Lactamase IMP-1

2020 ◽  
Vol 17 ◽  
Author(s):  
Yue-Juan Zhang ◽  
Le Zhai ◽  
Yi Wan ◽  
Ke-Wu Yang
Keyword(s):  
Antibiotic Resistance ◽  
Antimicrobial Activities ◽  
Docking Studies ◽  
Titration Calorimetry ◽  
Global Public Health ◽  
Inhibition Activity ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition

Background: : The appearance of antibiotic resistance caused by metallo-β-lactamases (MβLs) is a global public health threat. Developing MβLs inhibitor is an effective way to overcome antibiotic resistance. Recently, azolylthioacetamides were reported to be promising MβLs inhibitors. Methods:: Triazolylthioacetamides were synthesized and tested for inhibition activity against the purified MβL IMP-1. Antimicrobial activities of these inhibitors in combination with cefazolin were evaluated. Isothermal titration calorimetry (ITC) was employed to characterize the binding of the inhibitor to IMP-1, and their action mechanism was studied by molecular docking. Results and Discussion: : Twenty compounds exhibited specific inhibitory activity against IMP-1 with an IC50 value in the range of 3.1-62.5 μM. Eight of the compounds can restore the antibacterial efficacy of cefazolin against E. coli BL21 strain producing IMP-1 by 2-4 fold. ITC monitoring showed that 1c exhibited dose-dependent inhibition on IMP-1. Docking studies revealed that the triazole group in 1c and 2d played an essential role in the inhibition activity. Cytotoxicity assay showed that 1c and 2d have low toxicity in L929 mouse fibroblastic cells. Conclusion: : The triazolylthioacetamides are efficient inhibitors of IMP-1 in vitro and in vivo.

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