Mechanisms of the Antineoplastic Effects of New Fluoroquinolones in 2D and 3D Human Breast and Bladder Cancer Cell Lines
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ABSTRACT:
SUBMITTER: Ferrario N
PROVIDER: S-EPMC11201967 | biostudies-literature | 2024 Jun
REPOSITORIES: biostudies-literature
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Project description:IntroductionThe anticancer properties of fluoroquinolones and the high concentrations they achieve in urine may help in bladder cancer therapy. This study aimed to analyze the properties of 4 fluoroquinolones as potential candidates for supportive treatment of bladder cancer.MethodsComparative analyses were performed on the cytotoxic effects of norfloxacin, enrofloxacin, moxifloxacin, and ofloxacin on normal and cancer urothelial cell lines. In 2D culture, the cytotoxic properties of fluoroquinolones were evaluated using MTT assay, real-time cell growth analysis, fluorescence and light microscopy, flow cytometry, and molecular analysis. In 3D culture, the properties of fluoroquinolones were tested using luminescence assays and confocal microscopy.Results and discussionAll tested fluoroquinolones in 2D culture decreased the viability of both tested cell lines in a dose- and timedependent manner. Lower concentrations did not influence cell morphology and cytoskeletal organization. In higher concentrations, destruction of the actin cytoskeleton and shrinkage of the nucleus was visible. Flow cytometry analysis showed cell cycle inhibition of bladder cancer cell lines in the G2/M phase. This influence was minimal in the case of normal urothelium cells. In both tested cell lines, increases in the number of late apoptotic cells were observed. Molecular analysis showed variable expression of studied genes depending on the drug and concentration. In 3D culture, tested drugs were effective only in the highest tested concentrations which was accompanied by caspase 3/7 activation and cytoskeleton degradation. This effect was hardly visible in non-cancer cell lines. According to the data, norfloxacin and enrofloxacin had the most promising properties. These two fluoroquinolones exhibited the highest cytotoxic properties against both tested cell lines. In the case of norfloxacin, almost all calculated LC values for bladder cancer cell lines were achievable in the urine. Enrofloxacin and norfloxacin can be used to support chemotherapy in bladder cancer patients.
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Project description:The aim of this study was to investigate the effect and the mechanism of gamma linolenic acid (GLA) treatment on human hepatocellular (HCC) cell lines. The human HCC cell line HuH7 was exposed to GLA. Cell proliferation and reactive oxygen species (ROS) generation including lipid peroxidation and apoptosis were compared. We then used a cDNA microarray analysis to investigate the molecular changes induced by GLA. GLA treatment significantly reduced cell proliferation, generated ROS, and induced apoptosis. After 24 h exposure of Huh7 cells to GLA, we identified several genes encoding the antioxidant proteins to be upregulated: heme oxygenase-1 (HO-1), aldo-keto reductase 1 family C1 (AKR1C1), C4 (AKR1C4), and thioredoxin (Trx). The HO-1 protein levels were overexpressed in Huh7 cells after GLA exposure using a Western blot analysis. Furthermore, chromium mesoporphyrin (CrMP), an inhibitor of HO activity, significantly potentiated GLA cytotoxicity. GLA treatment has induced cell growth inhibition, ROS generation including lipid peroxidation, and HO-1 production for antioxidant protection against oxidative stress caused by GLA in Huh7 cells. GLA treatment should be considered as a therapeutic modality in patients with advanced HCC.
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Project description:A comparison of gene expression profiles for 25 breast cancer cell lines grown in 2D and 3D tissue culture conditions
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Project description:We examine the unusual dispersion and attenuation of transverse electromagnetic waves in the few-THz regime on nanoscale graphene and copper transmission lines. Conventionally, such propagation has been considered to be highly dispersive, due to the RC time constant-driven voltage diffusion below 1 THz and plasmonic effects at higher optical frequencies. Our numerical modeling across the microwave, THz, and optical frequency ranges reveals that the conductor kinetic inductance creates an ultra-broadband linear-dispersion and constant-attenuation region in the THz regime. This so-called LC region is an ideal characteristic that is known to be absent in macro-scale transmission lines. The kinetic-LC frequency range is dictated by the structural dimensionality and the free-carrier scattering rate of the conductor material. Moreover, up to 40x wavelength reduction is observed in graphene transmission lines.
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Project description:Background: Bladder cancer is the fourth most commonly diagnosed cancer among males worldwide. Current treatment strategies established for bladder cancer mainly consist of cystectomy yet advances in radiation therapy have pointed to the value of organ-preserving strategies in preserving patients' quality of life. Aim: To study and compare the radiosensitivity in two-dimension (2D) and physiologically-relevant three-dimension (3D) in vitro culture of three human bladder cancer cell lines, RT4, T24, and UM-UC-3. Materials and Methods: Clonogenic assay was performed to assess cells' radiosensitivity in 2D. Employing the 3D Matrigel™-based cultures to enrich for cancer stem cells (CSCs) allowed us to assess the survival of this subpopulation of cells via evaluating the number, i.e., sphere forming unit (SFU), and the sizes of cultured spheres, formed from cells exposed to different radiation doses compared to non-irradiated cells. Results: Irradiating cells with increasing radiation doses revealed highest survival rates with RT4 cells in 2D, followed by T24 and UM-UC-3. In 3D, however, UM-UC-3 cells were shown to be the most radio-resistant as evidenced by the number of spheres formed, yet they displayed the least efficient volume reduction/regression (VR), whilst the volume decreased significantly for both RT4 and T24 cells. Sphere VR and sphere ratio (SR) values were then plotted against each other demonstrating a linear correlation between volume and number with RT4 and UM-UC-3 cell lines, but not T24. Lastly, multiple regression model was employed to evaluate the possibility of obtaining a function combining both 3D parameters, SR and VR, with the surviving fraction (SF) in 2D, and showed a linear regression for T24 cells only, with a correlation coefficient of 0.97 for the combined parameters. Conclusion: We were able to radiobiologically characterize 3 human bladder cancer cell lines showing differential effects of radiation between 2D and 3D culture systems, paving the way for achieving better assessment of radiosensitivity of bladder cancer in vitro.
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Project description:* To compare surgical and oncological outcomes in patients underwent to colorectal resection with 3D vs 2D laparoscopic technique.
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Project description:Comparison of gene expression data between cell lines grown on 2D tissue culture plastic or 3D matrigel A427, A549, H23, H358, H460, H661, H1437, and H1703 cells were compared
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Project description:A comparison of gene expression profiles for 25 breast cancer cell lines grown in 2D and 3D tissue culture conditions
2007-05-02 | E-TABM-244 | biostudies-arrayexpress
Project description:Development of a reliable method for human triple-negative breast cancer organotypic culture: Improving imaging and genomic studies in 3D cultures The primary objectives of this study are to develop an advanced three-dimensional cell culture system to better model the tumor microenvironment in triple-negative breast cancer (TNBC), analyze the differences in molecular and cellular behavior between two-dimensional (2D) and 3D cultures, and investigate the impact of these differences on key oncogenic signaling pathways, specifically PI3K and β-catenin.
2024-09-20 | GSE277405 | GEO