Bacterial azurin in potential cancer therapy.
Ontology highlight
ABSTRACT:
SUBMITTER: Chakrabarty AM
PROVIDER: S-EPMC4957595 | biostudies-literature | 2016 Jul
REPOSITORIES: biostudies-literature
Publications
Bacterial azurin in potential cancer therapy.
Cell cycle (Georgetown, Tex.) 20160422 13
Similar Datasets
Project description:Azurin secreted by Pseudomonas aeruginosa is an anticancer bacteriocin, which preferentially enters human cancer cells and induces apoptosis or growth inhibition. It turns out that azurin is a multi-target anticancer agent interfering in the p53 signaling pathway and the non-receptor tyrosine kinases signaling pathway. This suggests that azurin exerts its anticancer activity by interacting with multiple targets and interfering in multiple steps in disease progression. Therefore, azurin could overcome resistance to therapy. Besides azurin, putative bacteriocins that possess functional properties similar to those of azurin have been identified in more bacteria species. A systematic investigation on the anticancer mechanisms of azurin and the azurin-like bacteriocins will provide more and better options in cancer therapy. In this review, we summarize how azurin and the derived peptides hijack key cellular regulators or cell surface receptors to remodel the cellular signaling networks. In particular, we highlight the necessity of determining the structure of azurin/p53 complex and investigating the influence of post-translational modifications on interactions between azurin and p53. Therapeutic applications of azurin and derived peptides are also discussed.
| S-EPMC5699490 | biostudies-literature
Project description:We performed a microarray analysis to compare the expression profile of azurin treated and untreated with different P-cadherin expression levels. We also compared the differentially expressed genes regulated by P-cadherin overexpression. Both cell lines presented an up-regulation of apoptosis mediated by p53 protein, endocytosis and vesicle-mediated transport. Conversely, invasive MCF-7/AZ.Pcad cells treated with azurin presented a decreased expression of genes associated with cell surface receptors and signal transduction, as well as genes associated with biological adhesion and migration. Azurin is a bacterial protein from Pseudomonas aeruginosa which exerts an inhibitory activity in cancer cells. In P-cadherin-overexpressing models, a bad prognosis marker in breast cancer increasing invasion and other malignant features, azurin decreases the invasion of cancer cells. We performed a microarray analysis to compare the expression profile of azurin treated cells with different P-cadherin expression levels. Azurin up-regulated apoptosis mediated by p53 protein, endocytosis and vesicle-mediated transport. In the contrary, in invasive MCF-7/AZ.Pcad cells, azurin decreased the expression of genes associated with cell surface receptors and signal transduction, as well as biological adhesion. Further, azurin decreased adhesion of cells to proteins from the Extracellular matrix (ECM) and altered protein expression of integrins α6, β4 and β1 and interfered with the ability of these cells to form mammospheres. Altogether, our results further enlighten the anti-cancer effects mediated by azurin in P-cadherin overexpression breast cancer models.
2014-04-30 | GSE54319 | GEO
Project description:Genetically engineered Salmonella Typhimurium are potent vectors for prophylactic and therapeutic measures against pathogens as well as cancer. This is based on the potent adjuvanticity that supports strong immune responses. The physiology of Salmonella is well understood. It simplifies engineering of both enhanced immune-stimulatory properties as well as safety features, thus, resulting in an appropriate balance between attenuation and efficacy for clinical applications. A major virulence factor of Salmonella is the flagellum. It is also a strong pathogen-associated molecular pattern recognized by extra- and intracellular receptors of immune cells of the host. At the same time, it represents a serious metabolic burden. Accordingly, the bacteria evolved tight regulatory mechanisms that control flagella synthesis in vivo. Here, we systematically investigated the immunogenicity and adjuvant properties of various flagella mutants of Salmonella in vitro and in a mouse cancer model in vivo. We found that mutants lacking the flagellum-specific ATPase FliHIJ or the inner membrane ring FliF displayed the greatest stimulatory capacity and strongest anti-tumor effects, while remaining safe in vivo. Scanning electron microscopy revealed the presence of outer membrane vesicles in the ΔfliF and ΔfliHIJ mutants. Finally, the combination of the ΔfliF and ΔfliHIJ mutations with our previously described attenuated and immunogenic background strain SF102 displayed strong efficacy against the highly resistant cancer cell line RenCa. We thus conclude that manipulating flagella biosynthesis has great potential for the construction of highly efficacious and versatile Salmonella vector strains.
2019-11-25 | GSE116623 | GEO
Project description:Salmonella typhimurium VNP-20009 (VNP) is a non-pathogenic attenuated strain, which, as a facultative anaerobe, preferentially accumulates in hypoxic regions of solid tumors. Here, VNP was utilized as a delivery vehicle of the anti-tumor protein Lipidated azurin, Laz, which is produced by the meningitis-causing bacterium Neisseria meningitides. In brain cancer cells, Laz has been demonstrated to induce apoptosis through an interaction with the tumor suppressor protein p53. In this study, the laz gene, including its signal sequence, was cloned downstream of a hypoxia inducible promoter (HIP-1), before being electroporated into VNP. Successful ectopic expression and export of the Laz protein by VNP under hypoxic conditions were confirmed by Western blot analysis of the cell-free culture medium. Effective expression of Laz by VNP was investigated in two glioblastoma cell lines: LN-229 and U-373, with the latter line carrying a mutated version of p53; as well as in the breast cancer line MCF-7. Cytotoxicity of the VNP-Laz was assessed by determining the fluorescence of the apoptotic marker caspases 3/7. Compared to the purified Laz, VNP-Laz, significantly induced apoptosis in MCF-7, LN-229 and, to a much lower extent in U-373 cells, suggesting a p53-linked mechanism. Our results might represent a new approach of targeted gene delivery and suggest a potential application in brain tumor therapy.
| S-EPMC7099546 | biostudies-literature
Project description:We performed a microarray analysis to compare the expression profile of azurin treated and untreated with different P-cadherin expression levels. We also compared the differentially expressed genes regulated by P-cadherin overexpression. Both cell lines presented an up-regulation of apoptosis mediated by p53 protein, endocytosis and vesicle-mediated transport. Conversely, invasive MCF-7/AZ.Pcad cells treated with azurin presented a decreased expression of genes associated with cell surface receptors and signal transduction, as well as genes associated with biological adhesion and migration. Azurin is a bacterial protein from Pseudomonas aeruginosa which exerts an inhibitory activity in cancer cells. In P-cadherin-overexpressing models, a bad prognosis marker in breast cancer increasing invasion and other malignant features, azurin decreases the invasion of cancer cells. We performed a microarray analysis to compare the expression profile of azurin treated cells with different P-cadherin expression levels. Azurin up-regulated apoptosis mediated by p53 protein, endocytosis and vesicle-mediated transport. In the contrary, in invasive MCF-7/AZ.Pcad cells, azurin decreased the expression of genes associated with cell surface receptors and signal transduction, as well as biological adhesion. Further, azurin decreased adhesion of cells to proteins from the Extracellular matrix (ECM) and altered protein expression of integrins M-NM-16, M-NM-24 and M-NM-21 and interfered with the ability of these cells to form mammospheres. Altogether, our results further enlighten the anti-cancer effects mediated by azurin in P-cadherin overexpression breast cancer models. Cells were exposed to azurin (100uM) for 48h, after which total RNA was extracted. Control cells were exposed during the same time to PBS buffer solution. Three independent samples for each condition were used treated with different azurin production batches.
2014-04-30 | E-GEOD-54319 | biostudies-arrayexpress
Project description:Tumor suppressor p53 prevents tumorigenesis by promoting cell cycle arrest and apoptosis through transcriptional regulation. Dysfunction of p53 occurs frequently in human cancers. Thus, p53 becomes one of the most promising targets for anticancer treatment. A bacterial effector protein azurin triggers tumor suppression by stabilizing p53 and elevating its basal level. However, the structural and mechanistic basis of azurin-mediated tumor suppression remains elusive. Here we report the atomic details of azurin-mediated p53 stabilization by combining X-ray crystallography with nuclear magnetic resonance. Structural and mutagenic analysis reveals that the p28 region of azurin, which corresponds to a therapeutic peptide, significantly contributes to p53 binding. This binding stabilizes p53 by disrupting COP1-mediated p53 ubiquitination and degradation. Using the structure-based design, we obtain several affinity-enhancing mutants that enable amplifying the effect of azurin-induced apoptosis. Our findings highlight how the structure of the azurin-p53 complex can be leveraged to design azurin derivatives for cancer therapy.
| S-EPMC9845241 | biostudies-literature
Project description:We performed a microarray analysis to compare the expression profile of azurin treated and untreated with different P-cadherin expression levels. We also compared the differentially expressed genes regulated by P-cadherin overexpression. Both cell lines presented an up-regulation of apoptosis mediated by p53 protein, endocytosis and vesicle-mediated transport. Conversely, invasive MCF-7/AZ.Pcad cells treated with azurin presented a decreased expression of genes associated with cell surface receptors and signal transduction, as well as genes associated with biological adhesion and migration. Azurin is a bacterial protein from Pseudomonas aeruginosa which exerts an inhibitory activity in cancer cells. In P-cadherin-overexpressing models, a bad prognosis marker in breast cancer increasing invasion and other malignant features, azurin decreases the invasion of cancer cells. We performed a microarray analysis to compare the expression profile of azurin treated cells with different P-cadherin expression levels. Azurin up-regulated apoptosis mediated by p53 protein, endocytosis and vesicle-mediated transport. In the contrary, in invasive MCF-7/AZ.Pcad cells, azurin decreased the expression of genes associated with cell surface receptors and signal transduction, as well as biological adhesion. Further, azurin decreased adhesion of cells to proteins from the Extracellular matrix (ECM) and altered protein expression of integrins α6, β4 and β1 and interfered with the ability of these cells to form mammospheres. Altogether, our results further enlighten the anti-cancer effects mediated by azurin in P-cadherin overexpression breast cancer models. Cells were exposed to azurin (100uM) for 48h, after which total RNA was extracted. Control cells were exposed during the same time to PBS buffer solution. Three independent samples for each condition were used treated with different azurin production batches.
| S-ECPF-GEOD-54319 | biostudies-other
Project description:Bacteria preferentially accumulating in tumor microenvironments can be utilized as natural vehicles for tumor targeting. However, neither current chemical nor genetic approaches alone can fully satisfy the requirements on both stability and high efficiency. Here, we propose a strategy of "charging" bacteria with a nano-photocatalyst to strengthen their metabolic activities. Carbon nitride (C3N4) is combined with Escherichia coli (E. coli) carrying nitric oxide (NO) generation enzymes for photo-controlled bacterial metabolite therapy (PMT). Under light irradiation, photoelectrons produced by C3N4 can be transferred to E. coli to promote the enzymatic reduction of endogenous NO3- to cytotoxic NO with a 37-fold increase. In a mouse model, C3N4 loaded bacteria are perfectly accumulated throughout the tumor and the PMT treatment results in around 80% inhibition of tumor growth. Thus, synthetic materials-remodeled microorganism may be used to regulate focal microenvironments and increase therapeutic efficiency.
| S-EPMC5920064 | biostudies-literature
Project description:Sorcin (Soluble resistance related calcium binding protein) is a small soluble penta EF family (PEF) of calcium (Ca2+) binding protein (22,000 Da). It has been reported to play crucial roles in the regulation of calcium homeostasis, apoptosis, vesicle trafficking, cancer development, and multidrug resistance (MDR). Overexpression of sorcin has been reported to be associated with different cancers such as breast cancer, colorectal cancer, gastric cancer, leukemia, lung cancer, nasopharyngeal cancer, ovarian cancer, etc. Essentially, expression of sorcin has been found to be elevated in cancer cells as compared to normal cells, indicating that it has prominent role in cancer. Moreover, sorcin was found to be the regulator of various proteins that has an association with carcinogenesis including NF-?B, STAT3, Akt, ERK1/2, VEGF, MMPs, caspases, etc. Sorcin was also found to regulate apoptosis, as silencing of the same resulted in increased levels of proapoptotic genes and induced mitochondrial apoptotic pathway in cancer. Interestingly, mutations in the sorcin gene have been closely linked with poor overall survival in bladder cancer, brain lower-grade glioma, glioblastoma, glioblastoma multiforme, kidney renal clear cell carcinoma, and stomach adenocarcinoma. Additionally, overexpression of sorcin was also found to induce MDR against different chemotherapeutic drugs. All these findings mark the importance of sorcin in cancer development and MDR. Therefore, there is urgent need to explore the functional mechanism of sorcin and to analyze whether silencing of sorcin would able to chemosensitize MDR cells. The current review summarizes the structure, expression, and functions of sorcin and its importance in the regulation of various malignancies and MDR.
| S-EPMC6134165 | biostudies-other
Project description:Methyl jasmonate (MeJa) is a naturally occurring hydrophobic oxylipin phytohormone. Early findings obtained from cancer cell lines suggest that MeJa is endowed with anticancer capabilities. It has been recently proposed that MeJa represents a novel agent that exhibits direct and selective actions against tumor cells without affecting normal human cells. In a previous study, I reported that MeJa itself is enough to result in the dysfunction of mitochondria and chloroplasts, as well as to activate cell death program (apoptosis), in the normal protoplasts of Arabidopsis thaliana. Indeed, this also holds true for other living plant systems in which senescence, hypersensitive response and oxidative stress have been found under MeJa action. Therefore, in this addendum to my previous article, I would like to stress that much more attention should be paid to the potential effect(s) of MeJa, or its derivatives, on healthy cells and tissues before it is used for clinical anticancer drugs, whether being used alone or in combination with other agents.
| S-EPMC4883903 | biostudies-other