scholarly journals A new synthetic spiroketal: studies on antitumor activity on murine melanoma model In vivo and mechanism of action In vitro

2018 ◽  
Author(s):  
Pietro Spanu ◽  
Maria Pia Fuggetta ◽  
Franco Morelli ◽  
Fausta Ulgheri ◽  
Francesco Deligia ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Mechanism Of Action ◽  
Murine Melanoma ◽  
Melanoma Model

A New Synthetic Spiroketal: Studies on Antitumor Activity on Murine Melanoma Model In Vivo and Mechanism of Action In Vitro

2019 ◽  
Vol 19 (4) ◽  
pp. 567-578
Author(s):  
Maria P. Fuggetta ◽  
Pietro Spanu ◽  
Fausta Ulgheri ◽  
Francesco Deligia ◽  
Paola Carta ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Growth ◽  
Antitumor Effect ◽  
Antitumor Efficacy ◽  
Murine Melanoma ◽  
Melanoma Model ◽  
High Antitumor Activity ◽  
Dose Dependent

Background:In a previous study, we synthesised a new spiroketal derivative, inspired to natural products, that has shown high antiproliferative activity, potent telomerase inhibition and proapoptotic activity on several human cell lines.Objective:This work focused on the study of in vivo antitumor effect of this synthetic spiroketal on a murine melanoma model. In order to shed additional light on the origin of the antitumor effect, in vitro studies were performed.Methods:Spiroketal was administered to B16F10 melanoma mice at a dose of 5 mg/Kg body weight via intraperitoneum at alternate days for 15 days. Tumor volume measures were made every 2 days starting after 12 days from cells injection. The effects of the spiroketal on tumor growth inhibition, apoptosis induction, and cell cycle modification were investigated in vitro on B16 cells. HIF1α gene expression, the inhibition of cells migration and the changes induced in cytoskeleton conformation were evaluated.Results:Spiroketal displayed proapoptotic activity and high antitumor activity in B16 cells with nanomolar IC50. Moreover it has shown to inhibit cell migration, to strongly reduce the HIF1α expression and to induce strongly deterioration of cytoskeleton structure. A potent dose-dependent antitumor efficacy in syngenic B16/C57BL/6J murine model of melanoma was observed with the suppression of tumor growth by an average of 90% at a dose of 5 mg/kg.Conclusion:The synthesized spiroketal shows high antitumor activity in the B16 cells in vitro at nM concentration and a dose-dependent antitumor efficacy in syngenic B16/C57BL/6J mice. The results suggest that this natural product inspired spiroketal may have a potential application in melanoma therapy.

Cytotoxic Effect of Spondias cytherea Fruit Extract in Murine Melanoma Model In Vivo and In Vitro

2018 ◽  
Vol 37 (3) ◽  
pp. 231-240
Author(s):  
Feudjio Ndemanou Yolande ◽  
Bhattacharyya Sayantan ◽  
Ghosh Paramita ◽  
Sarkar Deblina ◽  
Mouokeu Raymond Simplice ◽  
...  
Keyword(s):  
Cytotoxic Effect ◽  
Fruit Extract ◽  
Murine Melanoma ◽  
Melanoma Model

The Combi-Targeting Concept: Dissection of the Binary Mechanism of Action of the Combi-Triazene SMA41 in Vitro and Antitumor Activity in Vivo

2004 ◽  
Vol 311 (3) ◽  
pp. 1163-1170 ◽  
Author(s):  
Stephanie L. Matheson ◽  
James P. McNamee ◽  
Taiqui Wang ◽  
Moulay A. Alaoui-Jamali ◽  
Ana M. Tari ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Mechanism Of Action

scholarly journals In vitro and in vivo anticancer properties of a Calcarea carbonica derivative complex (M8) treatment in a murine melanoma model

BMC Cancer ◽  
2010 ◽  
Vol 10 (1) ◽  
Author(s):  
Fernando SF Guimarães ◽  
Lucas F Andrade ◽  
Sharon T Martins ◽  
Ana PR Abud ◽  
Reginaldo V Sene ◽  
...  
Keyword(s):  
Anticancer Properties ◽  
Murine Melanoma ◽  
Melanoma Model

ANTITUMOR EFFECT OF COLLOIDAL SILVER BISILICATE IN EXPERIMENTAL IN VITRO AND IN VIVO STUDIES

2019 ◽  
Vol 65 (5) ◽  
pp. 760-765
Author(s):  
Margarita Tyndyk ◽  
Irina Popovich ◽  
A. Malek ◽  
R. Samsonov ◽  
N. Germanov ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Human Tumor ◽  
Significant Inhibition ◽  
In Vivo Studies ◽  
Ehrlich Carcinoma ◽  
In Vivo Experiments

The paper presents the results of the research on the antitumor activity of a new drug - atomic clusters of silver (ACS), the colloidal solution of nanostructured silver bisilicate Ag6Si2O7 with particles size of 1-2 nm in deionized water. In vitro studies to evaluate the effect of various ACS concentrations in human tumor cells cultures (breast cancer, colon carcinoma and prostate cancer) were conducted. The highest antitumor activity of ACS was observed in dilutions from 2.7 mg/l to 5.1 mg/l, resulting in the death of tumor cells in all studied cell cultures. In vivo experiments on transplanted Ehrlich carcinoma model in mice consuming 0.75 mg/kg ACS with drinking water revealed significant inhibition of tumor growth since the 14th day of experiment (maximally by 52% on the 28th day, p < 0.05) in comparison with control. Subcutaneous injections of 2.5 mg/kg ACS inhibited Ehrlich's tumor growth on the 7th and 10th days of the experiment (p < 0.05) as compared to control.

scholarly journals Effect of ethanol and cocaine on [11C]MPC-6827 uptake in SH-SY5Y cells

2021 ◽  
Author(s):  
Naresh Damuka ◽  
Miranda Orr ◽  
Paul W. Czoty ◽  
Jeffrey L. Weiner ◽  
Thomas J. Martin ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Ex Vivo ◽  
Neuroblastoma Cells ◽  
Proper Function ◽  
Brain Functions ◽  
Biodistribution Studies ◽  
Positron Emission ◽  
Vitro Binding

AbstractMicrotubules (MTs) are structural units in the cytoskeleton. In brain cells they are responsible for axonal transport, information processing, and signaling mechanisms. Proper function of these processes is critical for healthy brain functions. Alcohol and substance use disorders (AUD/SUDs) affects the function and organization of MTs in the brain, making them a potential neuroimaging marker to study the resulting impairment of overall neurobehavioral and cognitive processes. Our lab reported the first brain-penetrant MT-tracking Positron Emission Tomography (PET) ligand [11C]MPC-6827 and demonstrated its in vivo utility in rodents and non-human primates. To further explore the in vivo imaging potential of [11C]MPC-6827, we need to investigate its mechanism of action. Here, we report preliminary in vitro binding results in SH-SY5Y neuroblastoma cells exposed to ethanol (EtOH) or cocaine in combination with multiple agents that alter MT stability. EtOH and cocaine treatments increased MT stability and decreased free tubulin monomers. Our initial cell-binding assay demonstrated that [11C]MPC-6827 may have high affinity to free/unbound tubulin units. Consistent with this mechanism of action, we observed lower [11C]MPC-6827 uptake in SH-SY5Y cells after EtOH and cocaine treatments (e.g., fewer free tubulin units). We are currently performing in vivo PET imaging and ex vivo biodistribution studies in rodent and nonhuman primate models of AUD and SUDs and Alzheimer's disease.

Surface Labeling with Adhesion Protein FimH Improves Binding of Immunotherapeutic Agent Salmonella Ty21a to the Bladder Epithelium

2020 ◽  
pp. 1-12
Author(s):  
Maroeska J. Burggraaf ◽  
Lisette Waanders ◽  
Mariska Verlaan ◽  
Janneke Maaskant ◽  
Diane Houben ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Antitumor Activity ◽  
Bladder Wall ◽  
Bladder Epithelium ◽  
Modest Improvement ◽  
Adhesion Protein ◽  
Survival Experiment ◽  
Muscle Invasive

BACKGROUND: Bladder cancer is the ninth most common cancer in men. 70% of these tumors are classified as non-muscle invasive bladder cancer and those patients receive 6 intravesical instillations with Mycobacterium bovis BCG after transurethral resection. However, 30% of patients show recurrences after treatment and experience severe side effects that often lead to therapy discontinuation. Recently, another vaccine strain, Salmonella enterica typhi Ty21a, demonstrated promising antitumor activity in vivo. Here we focus on increasing bacterial retention in the bladder in order to reduce the number of instillations required and improve antitumor activity. OBJECTIVE: To increase the binding of Ty21a to the bladder wall by surface labeling of the bacteria with adhesion protein FimH and to study its effect in a bladder cancer mouse model. METHODS: Binding of Ty21a with surface-labeled FimH to the bladder wall was analyzed in vitro and in vivo. The antitumor effect of a single instillation of Ty21a+FimH in treatment was determined in a survival experiment. RESULTS: FimH-labeled Ty21a showed significant (p <  0.0001) improved binding to mouse and human cell lines in vitro. Furthermore, FimH labeled bacteria showed ∼5x more binding to the bladder than controls in vivo. Enhanced binding to the bladder via FimH labeling induced a modest improvement in median but not in overall mice survival. CONCLUSIONS: FimH labeling of Ty21a significantly improved binding to bladder tumor cells in vitro and the bladder wall in vivo. The improved binding leads to a modest increase in median survival in a single bladder cancer mouse study.

scholarly journals Design, Synthesis, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitory Activity

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1838
Author(s):  
Naglaa M. Ahmed ◽  
Mahmoud M. Youns ◽  
Moustafa K. Soltan ◽  
Ahmed M. Said
Keyword(s):  
Molecular Modeling ◽  
Antitumor Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Antitumor Agents ◽  
Cancer Cell Lines ◽  
Normal Cells

Scaffolds hybridization is a well-known drug design strategy for antitumor agents. Herein, series of novel indolyl-pyrimidine hybrids were synthesized and evaluated in vitro and in vivo for their antitumor activity. The in vitro antiproliferative activity of all compounds was obtained against MCF-7, HepG2, and HCT-116 cancer cell lines, as well as against WI38 normal cells using the resazurin assay. Compounds 1–4 showed broad spectrum cytotoxic activity against all these cancer cell lines compared to normal cells. Compound 4g showed potent antiproliferative activity against these cell lines (IC50 = 5.1, 5.02, and 6.6 μM, respectively) comparable to the standard treatment (5-FU and erlotinib). In addition, the most promising group of compounds was further evaluated for their in vivo antitumor efficacy against EAC tumor bearing mice. Notably, compound 4g showed the most potent in vivo antitumor activity. The most active compounds were evaluated for their EGFR inhibitory (range 53–79 %) activity. Compound 4g was found to be the most active compound against EGFR (IC50 = 0.25 µM) showing equipotency as the reference treatment (erlotinib). Molecular modeling study was performed on compound 4g revealed a proper binding of this compound inside the EGFR active site comparable to erlotinib. The data suggest that compound 4g could be used as a potential anticancer agent.

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