scholarly journals In Vitro Antineoplastic and Antiviral Activity and In Vivo Toxicity of Geum urbanum L. Extracts

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 245
Author(s):  
Maya M. Zaharieva ◽  
Lyudmila L. Dimitrova ◽  
Stanislav Philipov ◽  
Ivanka Nikolova ◽  
Neli Vilhelmova ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Antiviral Activity ◽  
Cell Lines ◽  
Antineoplastic Activity ◽  
Liver Carcinoma ◽  
Type I ◽  
In Vivo Toxicity ◽  
Geum Urbanum

This study evaluated the in vitro antineoplastic and antiviral potential and in vivo toxicity of twelve extracts with different polarity obtained from the herbaceous perennial plant Geum urbanum L. (Rosaceae). In vitro cytotoxicity was determined by ISO 10993-5/2009 on bladder cancer, (T-24 and BC-3C), liver carcinoma (HEP-G2) and normal embryonic kidney (HEK-293) cell lines. The antineoplastic activity was elucidated through assays of cell clonogenicity, apoptosis induction, nuclear factor kappa B p65 (NFκB p65) activation and total glutathione levels. Neutral red uptake study was applied for antiviral activity. The most promising G. urbanum extract was analyzed by UHPLC–HRMS. The acute in vivo toxicity analysis was carried out following OEDC 423. The ethyl acetate extract of aerial parts (EtOAc-AP) exhibited the strongest antineoplastic activity on bladder cancer cell lines (IC50 = 21.33–25.28 µg/mL) by inducing apoptosis and inhibiting NFκB p65 and cell clonogenicity. EtOAc and n-butanol extracts showed moderate antiviral activity against human adenovirus type 5 and human simplex virus type I. Seventy four secondary metabolites (gallic and ellagic acid derivatives, phenolic acids, flavonoids, etc.) were identified in EtOAc-AP by UHPLC–HRMS. This extract induced no signs of acute toxicity in liver and kidney specimens of H-albino mice in doses up to 210 mg/kg. In conclusion, our study contributes substantially to the detailed pharmacological characterization of G. urbanum, thus helping the development of health-promoting phytopreparations.

scholarly journals Development and Characterization of siRNA Lipoplexes: Effect of Different Lipids, In Vitro Evaluation in Cancerous Cell Lines and In Vivo Toxicity Study

2014 ◽  
Vol 15 (6) ◽  
pp. 1630-1643 ◽  
Author(s):  
Nirav Khatri ◽  
Dipesh Baradia ◽  
Imran Vhora ◽  
Mohan Rathi ◽  
Ambikanandan Misra
Keyword(s):  
Cell Lines ◽  
Toxicity Study ◽  
In Vitro Evaluation ◽  
In Vivo Toxicity ◽  
Cancerous Cell

scholarly journals Circ-ZFR Promotes Progression of Bladder Cancer by Upregulating WNT5A Via Sponging miR-545 and miR-1270

2021 ◽  
Vol 10 ◽  
Author(s):  
Liping Luo ◽  
Pingping Miao ◽  
Yao Ming ◽  
Jie Tao ◽  
Hongchun Shen
Keyword(s):  
Bladder Cancer ◽  
Cell Lines ◽  
Pearson Correlation ◽  
Survival Rates ◽  
Circular Rna ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Novel Target

BackgroundBladder cancer is one of the most common cancers all over the world. CircZFR is a circular RNA and has been implicated in tumor generation and invasion. However, the exact role of circZFR in the development of bladder cancer (BCa) remains unknown. This study aimed to investigate the function of circZFR in BCa, and further to probe into the association between circ-ZFR, miR-545/miR-1270 and WNT5A.MethodsThe expression of circZFR in BCa was quantified by qRT-PCR and was positively correlated with the prognosis of BCa patients. Next, the stable knockdown of circZFR BCa cell lines was established and the resulting capacities of proliferation, migration and invasion were measured. The association of circZFR with miR-1270/miR-545 was predicted by circinteractome prediction, and was confirmed by luciferase assay as well as RNA pull down assay. Furthermore, miRNA inhibitors, WNT5A overexpression and Pearson correlation analysis were used to examine the relationship between circZFR, miR-1270/miR-545 and WNT5A.ResultsThe expression of CircZFR was up-regulated both in BCa tissues and in BCa cell lines, and was positively correlated with patient survival rates. Blocking of circZFR’s expression by RNA inhibitors suppressed the proliferation, migration and invasion of BCa cells both in vitro and in vivo. On the other hand, overexpression of target miRNA supported that circZFR directly interact with miR-545 and miR-1270. Moreover, we demonstrated that circZFR promotes the progression of BCa by upregulating WNT5A’s expression via sponging miR-545 and miR-1270.ConclusionsCircZFR promotes the proliferation, migration and invasion of BCa cells by upregulating WNT5A signaling pathway via sponging miR-545 and miR-1270. These results provide new insights into the molecular mechanism of circZFR in BCa progression, and more important, a novel target for BCa clinical treatment.

scholarly journals TSPAN7 Exerts Anti-Tumor Effects in Bladder Cancer Through the PTEN/PI3K/AKT Pathway

2021 ◽  
Vol 10 ◽  
Author(s):  
Xi Yu ◽  
Shenglan Li ◽  
Mingrui Pang ◽  
Yang Du ◽  
Tao Xu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Lines ◽  
Therapeutic Potential ◽  
Tumor Grade ◽  
Biological Properties ◽  
Akt Pathway ◽  
Dynamic Regulation ◽  
Potential Marker

The tetraspanin protein superfamily participate in the dynamic regulation of cellular membrane compartments expressed in a variety of tumor types, which may alter the biological properties of cancer cells such as cell development, activation, growth and motility. The role of tetraspanin 7 (TSPAN7) has never been investigated in bladder cancer (BCa). In this study, we aimed to investigate the biological function of TSPAN7 and its therapeutic potential in human BCa. First, via reverse transcription and quantitative real-time PCR (qRT-PCR), we observed downregulation of TSPAN7 in BCa tissues samples and cell lines and found that this downregulation was associated with a relatively high tumor stage and tumor grade. Low expression of TSPAN7 was significantly correlated with a much poorer prognosis for BCa patients than was high expression. Immunohistochemistry (IHC) showed that low TSPAN7 expression was a high-risk predictor of BCa patient overall survival. Furthermore, the inhibitory effects of TSPAN7 on the proliferation and migration of BCa cell lines were detected by CCK-8, wound-healing, colony formation and transwell assays in vitro. Flow cytometry analysis revealed that TSPAN7 induced BCa cell lines apoptosis and cell cycle arrest. In vivo, tumor growth in nude mice bearing tumor xenografts could be obviously affected by overexpression of TSPAN7. Western blotting showed that overexpression of TSPAN7 activated Bax, cleaved caspase-3 and PTEN but inactivated Bcl-2, p-PI3K, and p-AKT to inhibit BCa cell growth via the PTEN/PI3K/AKT pathway. Taken together, our study will help identify a potential marker for BCa diagnosis and supply a target molecule for BCa treatment.

scholarly journals Cordia americana: Evaluation of in vitro anti-herpes simplex virus activity and in vivo toxicity of leaf extracts

2021 ◽  
pp. 362-368
Author(s):  
Gislaine Franco de Moura- Costa ◽  
Gean Pier Panizzon ◽  
Thalita Zago Oliveira ◽  
Marco Antonio Costa ◽  
João Carlos Palazzo de Mello ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Biological Activities ◽  
Leaf Extracts ◽  
In Vivo Toxicity ◽  
Simplex Virus ◽  
Hsv 1

Herpes simplex virus (HSV) type 1 and type 2 are responsible for causing infections whose symptoms can vary from subclinical to severe manifestations. Cordia americana is a plant used by traditional communities for the treatment of wounds and diarrhoea, as well as infections like flu and syphilis. Scientific evidence has shown that, among other biological activities, the plant possesses antiviral properties; however, the evaluation of the in vivo toxicity of preparations of this plant is still lacking. This study assessed the in vitro anti-HSV-1 and anti-HSV-2 activity of a crude extract (CE) obtained from the leaves of C. americana, as well as its aqueous (FAq) and ethyl-acetate fractions (FAc). In addition, the in vivo toxicity of the FAq was assessed. The sulforhodamine B method was performed to determine the antiviral activity and the in vivo toxicity was evaluated according to Brazilian federal regulations. The CE, FAq, and FAc demonstrated antiviral activity against HSV-1 in vitro, presenting EC50 values of 7.0±1.4, 1.5±0.35, and 7.5±3.8, respectively. The FAq also had activity against HSV-2 with an EC50 of 11.8±1.02. The toxicological study of FAq in animals showed that it had very low toxicity. No death occurred during acute or subchronic experiments, where up to 5000 mg/kg and 150 mg/kg FAq were tested respectively; and there were no signs of toxicity in the subchronic test. The results of this study, in conjunction with further studies, pave the way for a potential topical treatment for skin and mucosal diseases, such as HSV-1 and HSV-2 infections

scholarly journals Curcumin as Treatment for Bladder Cancer: A Preclinical Study of Cyclodextrin-Curcumin Complex and BCG as Intravesical Treatment in an Orthotopic Bladder Cancer Rat Model

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
J. Falke ◽  
J. Parkkinen ◽  
L. Vaahtera ◽  
C. A. Hulsbergen-van de Kaa ◽  
E. Oosterwijk ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Urothelial Carcinoma ◽  
Cell Lines ◽  
Rat Model ◽  
Carcinoma Cell ◽  
Carcinoma Cell Lines ◽  
Intravesical Instillations ◽  
Urothelial Carcinoma Cell

Objective. To evaluate the antitumor effect of cyclodextrin-curcumin complex (CDC) on human and rat urothelial carcinoma cells in vitro and to evaluate the effect of intravesical instillations of CDC, BCG, and the combination in vivo in the AY-F344 orthotopic bladder cancer rat model. Curcumin has anticarcinogenic activity on urothelial carcinoma and is therefore under investigation for the treatment of non-muscle invasive bladder cancer. Curcumin and BCG share immunomodulating pathways against urothelial carcinoma. Methods. Curcumin was complexed with cyclodextrin to improve solubility. Four human urothelial carcinoma cell lines and the AY-27 rat cell line were exposed to various concentrations of CDC in vitro. For the in vivo experiment, the AY-27 orthotopic bladder cancer F344 rat model was used. Rats were treated with consecutive intravesical instillations of CDC, BCG, the combination of CDC+BCG, or NaCl as control. Results. CDC showed a dose-dependent antiproliferative effect on all human urothelial carcinoma cell lines tested and the rat AY-27 urothelial carcinoma cell line. Moreover, intravesical treatment with CDC and CDC+BCG results in a lower percentage of tumors (60% and 68%, respectively) compared to BCG (75%) or control (85%). This difference with placebo was not statistically significant (p=0.078 and 0.199, respectively). However, tumors present in the placebo and BCG-treated rats were generally of higher stage. Conclusions. Cyclodextrin-curcumin complex showed an antiproliferative effect on human and rat urothelial carcinoma cell lines in vitro. In the aggressive orthotopic bladder cancer rat model, we observed a promising effect of CDC treatment and CDC in combination with BCG.

ALL-associated JAK1 mutations confer hypersensitivity to the antiproliferative effect of type I interferon

Blood ◽  
2010 ◽  
Vol 115 (16) ◽  
pp. 3287-3295 ◽  
Author(s):  
Tekla Hornakova ◽  
Sabina Chiaretti ◽  
Muriel M. Lemaire ◽  
Robin Foà ◽  
Raouf Ben Abdelali ◽  
...  
Keyword(s):  
Cell Lines ◽  
Type I Interferon ◽  
Type I ◽  
Type I Ifn ◽  
Transcriptional Signature ◽  
Activating Mutations ◽  
Type I Ifns ◽  
Antitumorigenic Effect

Abstract Activating mutations in JAK1 have been reported in acute lymphoblastic leukemias (ALLs). In this study, we found a type I interferon (IFN) transcriptional signature in JAK1 mutation-positive human ALL samples. This signature was recapitulated in vitro by the expression of JAK1 mutants in BW5147 and BaF3 hematopoietic cell lines. Binding of JAK1 to the IFN receptor was essential because mutations in the FERM domain abrogated this effect. Beside the constitutive activation of the type I IFN signaling cascade, JAK1 mutations also strongly potentiated the response to IFN in vitro. Typically, the proliferation of cell lines expressing JAK1A634D was abrogated by type I IFNs. Interestingly, we found that different JAK1 mutations differentially potentiate responses to type I IFNs or to interleukin-9, another cytokine using JAK1 to mediate its effects. This suggests that the type of mutation influences the specificity of the effect on distinct cytokine receptor signaling. Finally, we also showed in an in vivo leukemia model that cells expressing JAK1A634D are hypersensitive to the antiproliferative and antitumorigenic effect of type I IFN, suggesting that type I IFNs should be considered as a potential therapy for ALL with JAK1-activating mutations.

In vitro and in vivo studies of the antineoplastic activity of copper (II) compounds against human leukemia THP-1 and murine melanoma B16-F10 cell lines

2016 ◽  
Vol 123 ◽  
pp. 128-140 ◽  
Author(s):  
Layla J.H. Borges ◽  
Érika S. Bull ◽  
Christiane Fernandes ◽  
Adolfo Horn ◽  
Nathalia F. Azeredo ◽  
...  
Keyword(s):  
Cell Lines ◽  
Antineoplastic Activity ◽  
In Vivo Studies ◽  
Human Leukemia ◽  
Murine Melanoma ◽  
Melanoma B16

scholarly journals NF-κB-Mediated Inhibition of Apoptosis Is Required for Encephalomyocarditis Virus Virulence: a Mechanism of Resistance in p50 Knockout Mice

1998 ◽  
Vol 72 (7) ◽  
pp. 5654-5660 ◽  
Author(s):  
Edward M. Schwarz ◽  
Cornel Badorff ◽  
Timothy S. Hiura ◽  
Rainer Wessely ◽  
Annette Badorff ◽  
...  
Keyword(s):  
Cell Lines ◽  
Knockout Mice ◽  
Defense Mechanism ◽  
Encephalomyocarditis Virus ◽  
Type I ◽  
Double Knockout ◽  
Physiological Importance ◽  
Infected Cells

ABSTRACT Apoptosis is a central host defense mechanism to eliminate virus-infected cells. Activation of NF-κB suppresses apoptosis following some types of stimulation in vitro. To test the physiological importance of this pathway in vivo, we studied murine encephalomyocarditis virus (EMCV) infection in mice and cell lines defective in NF-κB1 (p50) signaling. As previously reported, we find that all p50 knockout (p50 −/−) mice survive an EMCV infection that readily kills normal mice. By introducing the p50 mutation into interferon (IFN) type I receptor knockout (IFNRI −/−) mice, we find that this resistance is not mediated by IFN-β as previously thought. While no IFNRI −/− mice survive, the double-knockout mice survive 60% of the time. The survival is tightly linked to the animals’ ability to clear the virus from the heart in vivo. Using murine embryonic fibroblasts (MEF) derived from wild-type, p50 −/−, and p65 −/− embryos, we found that NF-κB is not required for the replication cycle of EMCV. However, during these experiments we observed that p50 −/− and p65 −/− MEF infected with EMCV undergo enhanced, premature cytotoxicity. Upon examination of this cell death, we found that EMCV infection induced both plasma membrane and nuclear changes typical of apoptosis in all cell lines. These apoptotic processes occurred in an accelerated and pronounced way in the NF-κB-defective cells, as soon as 6 h after infection, when virus is beginning to be released. Previously, only the RelA (p65) subunit of NF-κB has been shown to play a role in suppressing apoptosis. In our studies, we find that p50 is equally important in suppressing apoptosis during EMCV infection. Additionally, we show that suppression of apoptosis by NF-κB1 is required for EMCV virulence in vivo. The attenuation in p50 −/− mice can be explained by rapid apoptosis of infected cells which allows host phagocytes to clear infected cells before the viral burst leading to a reduction of the viral burden and survival of the mice.

ALL-Associated JAK1 Mutations Confer Hypersensitivity to the Anti-Proliferative Effect of Type I Interferon.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3066-3066
Author(s):  
Tekla Hornakova ◽  
Sabina Chiaretti ◽  
Muriel Lemaire ◽  
Robin Foà ◽  
Marco Tartaglia ◽  
...  
Keyword(s):  
Cell Lines ◽  
Type I Interferon ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Type I ◽  
Type I Ifn ◽  
Activating Mutations ◽  
Type I Ifns

Abstract Abstract 3066 Poster Board III-3 Recently, we and others reported activating mutations in JAK1 in acute lymphoblastic leukemia (ALL). These mutations are relatively common in adult patients with T cell ALL. JAK1 is a tyrosine kinase that associates to different cytokine receptors to mediate signal transduction. The associations of the mutant JAK1 with receptors like IL-2R or IL-9R are necessary to promote tumorigenicity by inducing constitutive signaling via the activation of the receptor complex. Because JAK1 mutations confer poor prognosis to the patients, there is a need for new therapies that could specifically target the leukemic blast. Starting from patient samples, we show here that JAK1-mutant ALL blasts are characterized by a type-I interferon (IFN) transcriptional signature. This signature was recapitulated in vitro by the expression of JAK1 mutants in BW5147 and BaF3 hematopoietic cell lines. Binding of JAK1 to the IFN receptor was essential since mutations in the FERM domain abrogated this effect. Beside the constitutive activation of the type I IFN signaling cascade, JAK1 mutations also strongly potentiated the response to IFN in vitro. Typically, the proliferation of cell lines expressing JAK1A634D was abrogated by type I IFNs. Interestingly, we found that different JAK1 mutations differentially potentiate responses to type I IFNs or to IL-9, another cytokine using JAK1 to mediate its effects. This suggests that the type of mutation influences the specificity of the effect on distinct cytokine receptor signaling. Finally, we also showed in an in vivo leukemia model that cells expressing JAK1A634D are hypersensitive to the anti-proliferative and anti-tumorigenic effect of type I IFN, suggesting that type I IFNs should be considered as a potential therapy for ALL with JAK1 activating mutations. Disclosures No relevant conflicts of interest to declare.

Molecular characterization of temsirolimus-induced response in human renal and bladder cancer cell lines.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 295-295
Author(s):  
Axel S. Merseburger ◽  
Mario W. Kramer ◽  
Hossein Tezval ◽  
Markus Kuczyk ◽  
Juergen Serth
Keyword(s):  
Bladder Cancer ◽  
Real Time ◽  
Cell Lines ◽  
Cancer Cell ◽  
Expression Patterns ◽  
Impedance Analysis ◽  
Bladder Cancer Cell ◽  
Tumor Entities

295 Background: Targeted therapies like mTOR inhibition is a clinically esthablished treatment modality for advanced renal cell cancer (RCC). We hypothesize that common elements of molecular signalling exists in RCC and transitional cell carcinoma of the bladder (TCC) that could provide a rational of the usage of this novel compound in human TCC. Therefore the goal of this investigation was to measure the in vivo and in vitro effect of temsirolimus/CCI-779 on human RCC and TCC cell lines on the molecular level. Methods: For in vivo experiments 3 RCC (786-O, A498, ACHN) cell lines and 7 TCC (T24, 5637, RT112, EJ-28, CLS-439, HB-CLS-1, HB-CLS-2) cell lines were compared. Effect of temsirolimus/CCI-779 was measured by real time impedance analysis (XCelligence, Roche). Following mRNA isolation microarray based mRNA expression analysis with 45.015 oligoprobes (G4112F, Agilent Technologies) was performed for molecular comparison of RCC and TCC cell lines. Expression patterns of 15 pathways were analyzed using the statistical software R (2.12.0) and the LIMMA package. Results: RCC and TCC cell lines demonstrated dose dependent inhibition of cellular growth with IC50 values of 10-20nM of temsirolimus/CCI-779 as measured by quantitative real time impedance analysis. Furthermore six out of 15 pathways including the mTOR and VEGF signalling were found with similar expression patterns following treatment with CCI-779 in both tumor entities. Conclusions: In vivo and in vitro analysis of temsirolimus mTOR inhitibtion on human bladder cancer cell lines support the hypothesis that a common molecular architectur exists in both tumor entities suggesting inhibition of mTOR in TCC as a possible target for further experimental therapeutic studies.

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