Bacterial proteins and peptides in cancer therapy

Chakrabarty, Ananda M.; Bernardes, Nuno; Fialho, Arsénio M.

doi:10.4161/bioe.29266

Cited by 45 publications

(30 citation statements)

References 54 publications

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“…6,7 Azurin is therefore expected to be a potential drug for cancer therapy. 8,9 The precursor form of azurin (148 residues) produced by P. aeruginosa is converted to a mature form (Paz, 128 residues) through the release of a signal peptide (20 residues) across the inner membrane (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Structural studies on Laz, a promiscuous anticancer Neisserial protein

et al. 2015

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Azurin and Laz (lipidated azurin) are 2 bacterial proteins with anticancer, anti-viral and anti-parasitic activities. Azurin, isolated from the bacterium Pseudomonas aeruginosa, termed Paz, demonstrates anticancer activity against a range of cancers but not against brain tumors. In contrast, Laz is produced by members of Gonococci/Meningococci, including Neisseria meningitides which can cross the blood-brain barrier to infect brain meninges. It has been previously reported that Laz has an additional 39 amino acid moiety, called an H.8 epitope, in the N-terminal part of the azurin moiety that allows Laz to cross the entry barrier to brain tumors such as glioblastomas. Exactly, how the H.8 epitope helps the azurin moiety of Laz to cross the entry barriers to attack glioblastoma cells is unknown. In this paper, we describe the structural features of the H.8 moiety in Laz using X-ray crystallography and demonstrate that while the azurin moiety of Laz adopts a b-sandwich fold with 2 b-sheets arranged in the Greek key motif, the H.8 epitope was present as a disordered structure outside the Greek key motif. Structures of Paz and H.8 epitope-deficient Laz are well superimposed. The structural flexibility of the H.8 motif in Laz explains the extracellular location of Laz in Neisseria where it can bind the key components of brain tumor cells to disrupt their tight junctions and allow entry of Laz inside the tumors to exert cytotoxicity.

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Section: Introductionmentioning

confidence: 99%

Structural studies on Laz, a promiscuous anticancer Neisserial protein

et al. 2015

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“…8. By this method, Azurin much more effectively enters the tumor cells than into the healthy 18,19 . Azurin induces apoptosis and works as promising anti-cancer agent.…”

Section: Resultsmentioning

confidence: 99%

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2018

IJPSR

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The pretentious extract of Pseudomonas aeruginosa has shown promising anticancer activity. It contains a protein called Azurin. It has a molecular weight of 14 kDa. It is soluble in water. It is a type I coppercontaining protein of cupredoxin family. In this work, Pseudomonas aeruginosa MTCC strain 647 was cultivated in modified Asparagine-proline broth. An attempt was done to isolate and purify azurin from Pseudomonas aeruginosa (MTCC 647) by using chromatography on sephadex G, CM cellulose and SDS PAGE electrophoresis. Recent studies have found that Pseudomonas aeruginosa can synthesize nano particles through either intracellular or extracellular mechanisms by bio synthetic means. Hence, the composite nano particles (Azurin-Ag NP) were synthesized by biosynthetic methods. P. aeruginosa MTCC strains 647 was cultivated in modified Asparagine-proline broth initially to produce shake flask cultures and then fed batch cultivation. From the bacterial extracted Azurin is isolated and purified to get a final concentration of 4.6 mg/g dry bacteria. As the nano particle mediated drug delivery effectively deliver the drug to the tumor cells, the composite nano particles (Azurin-Ag NP) were synthesized by biosynthetic methods. These bio synthetically produced Ag nano particles has loaded maximum 36 ng of Azurin protein. Pseudomonas aeruginosa MTCC strains 647 can be chosen as strain to produce Azurin in large scale. The anti-cancer activity of azurin is complimented with bio synthetic production of silver nano particles containing Azurin (Azurin-Ag-NPs). INTRODUCTION: Cancer treatment is done by radiation, chemotherapy, surgery and immunotherapy. Microorganisms and their products are found to prevent cancer regression with a remarkable anti-cancer activity 1 .

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“…Azurin is a multifunctional protein that induces apoptosis of cancerous cells, inhibits receptor tyrosine kinase-mediated cell signaling and angiogenesis, and is a promising tumoricidal protein 43, 44, 45. Azurin stabilizes p53 by forming a complex and protecting it from undergoing ubiquitination and proteasomal degradation 46, 47.…”

Section: Introductionmentioning

confidence: 99%

Bacterial Carriers for Glioblastoma Therapy

Mehta

Lyon

Patil

et al. 2017

Molecular Therapy - Oncolytics

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Treatment of aggressive glioblastoma brain tumors is challenging, largely due to diffusion barriers preventing efficient drug dosing to tumors. To overcome these barriers, bacterial carriers that are actively motile and programmed to migrate and localize to tumor zones were designed. These carriers can induce apoptosis via hypoxia-controlled expression of a tumor suppressor protein p53 and a pro-apoptotic drug, Azurin. In a xenograft model of human glioblastoma in rats, bacterial carrier therapy conferred a significant survival benefit with 19% overall long-term survival of >100 days in treated animals relative to a median survival of 26 days in control untreated animals. Histological and proteomic analyses were performed to elucidate the safety and efficacy of these carriers, showing an absence of systemic toxicity and a restored neural environment in treated responders. In the treated non-responders, proteomic analysis revealed competing mechanisms of pro-apoptotic and drug-resistant activity. This bacterial carrier opens a versatile avenue to overcome diffusion barriers in glioblastoma by virtue of its active motility in extracellular space and can lead to tailored therapies via tumor-specific expression of tumoricidal proteins.

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Bacterial proteins and peptides in cancer therapy

Cited by 45 publications

References 54 publications

Structural studies on Laz, a promiscuous anticancer Neisserial protein

Structural studies on Laz, a promiscuous anticancer Neisserial protein

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Bacterial Carriers for Glioblastoma Therapy

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