thiostrepton has been researched along with Neoplasms* in 7 studies
1 review(s) available for thiostrepton and Neoplasms
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Thiostrepton, a natural compound that triggers heat shock response and apoptosis in human cancer cells: a proteomics investigation.
Thiostrepton is a natural antibiotic produced by bacteria of Streptomyces genus. We identified Thiostrepton as a strong hit in a cell-based small molecule screen for DIAP1 stability modulators. It was shown previously that Thiostrepton induces upregulation of several gene products in Streptomyces lividans, including the TipAS and TipAL isoforms, and that it can induce apoptotic cell death in human cancer cells. Furthermore, it was suggested that thiostrepton induces oxidative and proteotoxic stress, as inferred from the transcriptional upregulation of stress-related genes and endoplasmic reticulum (ER) stress genes. We used a combination of biochemical and proteomics approaches to investigate the effect of Thiostrepton and other compounds in human cells. Our mass-spectrometry data and subsequent biochemical validation shows that Thiostrepton (and MG-132 proteasome inhibitor) trigger upregulation of heat shock proteins HspA1A, Hsp70, Hsp90α, or Hsp105 in various human cancer cells. We propose a model where Thiostrepton-induced proteasome inhibition leads to accumulation of protein aggregates that trigger a heat shock response and apoptosis in human cancer cells. Topics: Animals; Anti-Bacterial Agents; Apoptosis; Endoplasmic Reticulum Stress; Gene Expression Regulation, Neoplastic; Heat-Shock Proteins; Heat-Shock Response; Humans; Neoplasm Proteins; Neoplasms; Proteomics; Streptomyces lividans; Thiostrepton; Up-Regulation | 2014 |
6 other study(ies) available for thiostrepton and Neoplasms
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Engineered Near-Infrared Fluorescent Protein Assemblies for Robust Bioimaging and Therapeutic Applications.
Fluorescent proteins are investigated extensively as markers for the imaging of cells and tissues that are treated by gene transfection. However, limited transfection efficiency and lack of targeting restrict the clinical application of this method rooted in the challenging development of robust fluorescent proteins for in vivo bioimaging. To address this, a new type of near-infrared (NIR) fluorescent protein assemblies manufactured by genetic engineering is presented. Due to the formation of well-defined nanoparticles and spectral operation within the phototherapeutic window, the NIR protein aggregates allow stable and specific tumor imaging via simple exogenous injection. Importantly, in vivo tumor metastases are tracked and this overcomes the limitations of in vivo imaging that can only be implemented relying on the gene transfection of fluorescent proteins. Concomitantly, the efficient loading of hydrophobic drugs into the protein nanoparticles is demonstrated facilitating the therapy of tumors in a mouse model. It is believed that these theranostic NIR fluorescent protein assemblies, hence, show great potential for the in vivo detection and therapy of cancer. Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Drug Carriers; Genetic Engineering; Humans; Liver Neoplasms; Luminescent Proteins; Mice; Nanoparticles; Neoplasms; Peptides; Polyethylene Glycols; Spectroscopy, Near-Infrared; Thiostrepton; Transplantation, Heterologous | 2020 |
Autophagy induction by thiostrepton improves the efficacy of immunogenic chemotherapy.
Immunogenic cell death (ICD) is a peculiar modality of cellular demise that elicits adaptive immune responses and triggers T cell-dependent immunity.. Fluorescent biosensors were employed for an unbiased drug screen approach aiming at the identification of ICD enhancers.. Here, we discovered thiostrepton as an enhancer of ICD able to boost chemotherapy-induced ATP release, calreticulin exposure and high-mobility group box 1 exodus. Moreover, thiostrepton enhanced anticancer immune responses of oxaliplatin (OXA) in vivo in immunocompetent mice, yet failed to do so in immunodeficient animals. Consistently, thiostrepton combined with OXA altered the ratio of cytotoxic T lymphocytes to regulatory T cells, thus overcoming immunosuppression and reinstating anticancer immunosurveillance.. Altogether, these results indicate that thiostrepton can be advantageously combined with chemotherapy to enhance anticancer immunogenicity. Topics: Animals; Anti-Bacterial Agents; Antineoplastic Agents; Autophagy; Calreticulin; Cell Line, Tumor; Disease Models, Animal; Female; HMGB1 Protein; Humans; Immunogenic Cell Death; Mice; Mice, Inbred C57BL; Neoplasms; Oxaliplatin; T-Lymphocytes, Cytotoxic; Thiostrepton | 2020 |
Autophagy induction by thiostrepton for the improvement of anticancer therapy.
Macroautophagy/autophagy induction by caloric restriction mimetics (CRMs) is a strategy to stimulate anticancer immune responses of immunogenic cell death (ICD)-inducing chemotherapeutics. We designed a phenotypic screening campaign in which we identified pharmacological agents that have CRM properties (i.e., non-cytotoxic induction of autophagic flux that reduces cytoplasmic protein acetylation) and simultaneously act as ICD amplifiers (i.e. with the capacity to enhance the release of adenosine triphosphate, ATP, from stressed and dying cancer cells). This approach led to the identification of thiostrepton, a natural cyclic oligopeptide antibiotic, as an agent that enhances chemotherapy-induced anticancer immune responses in vivo, in immunocompetent mice bearing syngeneic tumors. Interestingly, both the pro-autophagic and the anticancer effects of thiostrepton rely on the activation of TFEB (transcription factor EB) and TFE3 (transcription factor E3). In summary, thiostrepton represents a novel CRM and ICD amplifier that may be useful for cancer therapy. Topics: Acetylation; Animals; Autophagy; Caloric Restriction; Mice; Neoplasms; Thiostrepton | 2020 |
Proteasome inhibitors induce p53-independent apoptosis in human cancer cells.
Proteasome inhibitors are used against human cancer, but their mechanisms of action are not entirely understood. For example, the role of the tumor suppressor p53 is controversial. We reevaluated the role of p53 in proteasome inhibitor-induced apoptosis by using isogenic human cancer cell lines with different p53 status. We found that well-known proteasome inhibitors such as MG132 and bortezomib, as well as the recently discovered proteasome inhibitor thiostrepton, induced p53-independent apoptosis in human cancer cell lines that correlated with p53-independent induction of proapoptotic Noxa but not Puma protein. In addition, these drugs inhibited growth of several cancer cell lines independently of p53 status. Notably, thiostrepton induced more potent apoptosis in HepG2 cells with p53 knockdown than in parental cells with wild-type p53. Our data confirm that proteasome inhibitors generally induce p53-independent apoptosis in human cancer cells. Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cysteine Proteinase Inhibitors; Humans; Neoplasms; Proteasome Inhibitors; Thiostrepton; Tumor Suppressor Protein p53 | 2011 |
Thiazole antibiotic thiostrepton synergize with bortezomib to induce apoptosis in cancer cells.
Thiazole antibiotic, thiostrepton was recently identified as proteasome inhibitor. We investigated the therapeutic potential of the combination of thiostrepton and proteasome inhibitor bortezomib (Velcade) on various human tumor cell lines. Combination of sub-lethal concentrations of thiostrepton and bortezomib induced potent apoptosis and inhibition of long-term colony formation in a wide variety of human cancer cell lines. The synergistic relationship between thiostrepton and bortezomib combination was also quantitatively demonstrated by calculating their combination index values that were much lower than 1 in all studied cell lines. The synergy between these drugs was based on their proteasome inhibitory activities, because thiostrepton modification, thiostrepton methyl ester, which did not have intact quinaldic acid ring and did not inhibit proteasome activity failed to demonstrate any synergy in combination with bortezomib. Topics: Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Boronic Acids; Bortezomib; Cell Line, Tumor; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drug Synergism; HCT116 Cells; Humans; Neoplasms; Pyrazines; Thiazoles; Thiostrepton | 2011 |
Micelle-encapsulated thiostrepton as an effective nanomedicine for inhibiting tumor growth and for suppressing FOXM1 in human xenografts.
The thiazole antiobiotic, thiostrepton, has been found to induce cell death in cancer cells through proteasome inhibition. As a proteasome inhibitor, thiostrepton has also been shown to suppress the expression of FOXM1, the oncogenic forkhead transcription factor overexpressed in cancer cells. In this study, we explored the potential in vivo anticancer properties of thiostrepton, delivered through nanoparticle encapsulation to xenograft models of breast and liver cancer. We encapsulated thiostrepton into micelles assembled from amphiphilic lipid-PEG (polyethylene glycol) molecules, where thiostrepton is solubilized within the inner lipid compartment of the micelle. Upon assembly, hydrophobic thiostrepton molecules are solubilized into the lipid component of the micelle shell, formed through the self-assembly of amphipilic lipid-PEG molecules. Maximum accumulation of micelle-thiostrepton nanoparticles (100 nm in diameter, -16 mV in zeta potential) into tumors was found at 4 hours postadministration and was retained for at least 24 hours. Upon continuous treatment, we found that nanoparticle-encapsulated thiostrepton reduced tumor growth rates of MDA-MB-231 and HepG2 cancer xenografts. Furthermore, we show for the first time the in vivo suppression of the oncogenic FOXM1 after treatment with proteasome inhibitors. Immunoblotting and immunohistochemical staining also showed increased apoptosis in the treated tumors, as indicated by cleaved caspase-3 expression. Our data suggest that the thiazole antibiotic/proteasome inhibitor thiostrepton, when formulated into nanoparticles, may be highly suited as a nanomedicine for treating human cancer. Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Down-Regulation; Drug Compounding; Forkhead Box Protein M1; Forkhead Transcription Factors; Hep G2 Cells; Humans; Male; Mice; Mice, Nude; Micelles; Models, Biological; Nanomedicine; Neoplasms; Thiostrepton; Treatment Outcome; Xenograft Model Antitumor Assays | 2011 |