digitonin has been researched along with Neoplasms* in 5 studies
5 other study(ies) available for digitonin and Neoplasms
Article | Year |
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Time- and Dose-Dependent Toxicity Studies in 3D Cultures Using a Luminescent Lactate Dehydrogenase Assay.
Three-dimensional (3D) in vitro systems closely resemble tissue microenvironments and provide predictive models for studying cytotoxic drug responses. The ability to capture the kinetic profiles of such responses in a dynamic and noninvasive way can further advance the utility of 3D cell cultures. Here, we describe the use of a luminescent lactate dehydrogenase (LDH) toxicity assay for monitoring time- and dose-dependent effects of drug treatment in 3D cancer spheroids. HCT116 spheroids formed in 96-well ultralow attachment plates were treated with increasing drug concentrations. Medium samples were collected at different timepoints, frozen, stored, and analyzed at the end of experiments using the luminescent LDH-Glo™ Assay. High assay sensitivity and low volume sampling enabled drug-induced toxicity profiling in a time- and dose-dependent manner. Topics: Antineoplastic Agents; Digitonin; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Indicators and Reagents; L-Lactate Dehydrogenase; Luminescent Measurements; Neoplasms; Spheroids, Cellular; Time Factors; Toxicity Tests; Tumor Cells, Cultured | 2021 |
Macromolecular crowding effect is critical for maintaining SIRT1's nuclear localization in cancer cells.
SIRT1 is a principle class III histone deacetylase which exhibits versatile functions in stress response, development, and pathological processes including cancer. Although SIRT1 deacetylates a wide range of nuclear and cytoplasmic proteins, its subcellular localization in cancer cells has been controversial. In this study, we uncovered the inconsistent reports about SIRT1 subcellular localization is partially due to different analysis approaches. While immunofluorescence and live cell imaging reveal a predominant nuclear localization of SIRT1, conventional cell fractionation often results in a severe leaking of SIRT1 into the cytoplasm. Such a leakage is mainly caused by loss of cytoplasmic macromolecular crowding effect as well as hypotonic dwelling during the isolation of the nuclei. We also developed an improved cell fractionation procedure which maintains SIRT1 in its original subcellular localization. Analyzing a variety of human cancer cell lines using this approach and other methods demonstrate that SIRT1 predominantly localizes to the nucleus in cancer cells. Topics: Cell Line, Tumor; Cell Nucleus; Chemical Fractionation; Digitonin; Ficoll; Humans; Hypotonic Solutions; Macromolecular Substances; Neoplasms; Sirtuin 1; Subcellular Fractions | 2016 |
Digitonin synergistically enhances the cytotoxicity of plant secondary metabolites in cancer cells.
In phytotherapy, extracts from medicinal plants are employed which contain mixtures of secondary metabolites. Their modes of action are complex because the secondary metabolites can react with single or multiple targets. The components in a mixture can exert additive or even synergistic activities. In this study, the cytotoxicity of some phytochemicals, including phenolics (EGCG and thymol), terpenoids (menthol, aromadendrene, β-sitosterol-O-glucoside, and β-carotene) and alkaloids (glaucine, harmine, and sanguinarine) were investigated alone or in combination with the cytotoxic monodesmosidic steroidal saponin digitonin in Caco-2, MCF-7, CEM/ADR5000, and CCRF-CEM cells. Digitonin was combined in non-toxic concentrations (5μM in each cell line; except in MCF-7 the concentration was 2μM), together with a selection of phenolics, terpenoids, and alkaloids to evaluate potential synergistic or additive effects. An enhanced cytotoxicity was observed in most combinations. Even multi-drug resistant (MDR) cells (such as CEM/ADR5000 cells), with a high expression of P-glycoprotein, were responsive to combinations. Sanguinarine was the most cytotoxic alkaloid against CEM/ADR5000, MCF-7, and CCRF-CEM cells alone and in combination with digitonin. As compared to sanguinarine alone, the combination was 44.53-, 15.38-, and 6.65-fold more toxic in each cell line, respectively. Most combinations synergistically increased the cytotoxicity, stressing the importance of synergy when using multi-target drugs and mixtures in phytotherapy. Topics: Alkaloids; Antineoplastic Agents, Phytogenic; ATP Binding Cassette Transporter, Subfamily B, Member 1; Benzophenanthridines; Caco-2 Cells; Digitalis; Digitonin; Drug Resistance, Multiple; Drug Synergism; Female; Humans; Isoquinolines; MCF-7 Cells; Neoplasms; Phenols; Phytotherapy; Plant Extracts; Terpenes | 2012 |
Synergism of three-drug combinations of sanguinarine and other plant secondary metabolites with digitonin and doxorubicin in multi-drug resistant cancer cells.
We determined the ability of some phytochemicals, including alkaloids (glaucine, harmine, and sanguinarine), phenolics (EGCG and thymol), and terpenoids (menthol, aromadendrene, β-sitosterol-O-glucoside, and β-carotene), alone or in combination with the saponin digitonin to reverse the relative multi-drug resistance of Caco-2 and CEM/ADR5000 cells to the chemotherapeutical agent doxorubicin. The IC(50) of doxorubicin in Caco-2 and CEM/ADR5000 was 4.22 and 44.08μM, respectively. Combination of non-toxic concentrations of individual secondary metabolite with doxorubicin synergistically sensitized Caco-2 and CEM/ADR5000 cells, and significantly enhanced the cytotoxicity of doxorubicin. Furthermore, three-drug combinations (secondary metabolite+digitonin+doxorubicin) were even more powerful. The best synergist was the benzophenanthridine alkaloid sanguinarine. It reduced the IC(50) value of doxorubicin 17.58-fold in two-drug combinations (sanguinarine+doxorubicin) and even 35.17-fold in three-drug combinations (sanguinarine+digitonin+doxorubicin) in Caco-2 cells. Thus synergistic drug combinations offer the possibility to enhance doxorubicin efficacy in chemotherapy. Topics: Alkaloids; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Benzophenanthridines; Caco-2 Cells; Digitonin; Doxorubicin; Drug Resistance, Neoplasm; Drug Synergism; Humans; Inhibitory Concentration 50; Isoquinolines; Neoplasms; Phenols; Phytotherapy; Plant Extracts; Plants; Terpenes | 2012 |
High resolution of human lactate dehydrogenase: new multiple forms and potential tumor markers.
Human lactate dehydrogenase (LDH) was investigated by ultrathin-layer polyacrylamide gel isoelectric focusing (IEF). In serum, approximately 15 bands and in lyzates of erythrocytes approximately 20 bands were detected. Known LDH isoenzymes (identified by markers) appeared in the zymograms as follows: LDH-1 as a single or double band, LDH-2 as a single band in serum and in the marker, and as a double band in hemolyzate, LDH-3 as a double band, and LDH-4 and LDH-5 each as a single band. LDH-1 was partly inactivated, probably due to deamidation in the acidic range of the pH gradient. Potential LDH tumor markers were detected in different tumor cytosols. Topics: Biomarkers, Tumor; Cytosol; Digitonin; Humans; Isoelectric Focusing; L-Lactate Dehydrogenase; Neoplasms | 1988 |