Anticancer Peptides: Prospective Innovation in Cancer Therapy

Gaspar, Diana; Castanho, Miguel A. R. B.

doi:10.1007/978-3-319-32949-9_4

Cited by 9 publications

(5 citation statements)

References 87 publications

(127 reference statements)

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“…The antimicrobial and anticancer activity of these HDPs has largely been attributed to their ability to bind and destabilize cell membranes. Such HDPs are attracting significant interest as potential novel antibiotics and as alternatives to conventional cancer chemotherapy based on their selectivity and proposed lower likelihood to generate acquired resistance (3, 5–7).…”

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confidence: 99%

“…The ABBREVIATIONS: AHDF, human adult dermal fibroblasts; CS-ab, cysteine-stabilized2ab; CTPP, C-terminal propeptide; ER, endoplasmic reticulum; HBD, human b-defensin; HDP, host defense peptide; HeLa, human cervical adenocarcinoma; IC 50 , half maximal inhibitory concentration; MM170, human malignant melanoma; MtDef, Medicago truncatula defensin; NaD1, Nicotiana alata defensin 1; NoD173, Nicotiana occidentalis defensin 173; NoD173 (A5R), NoD173 with the substitution of A5 with arginine; NoD173(Q22K), NoD173 with the substitution of Q22 with lysine; NoD173 R&A , reduced and alkylated NoD173; NsD7, Nicotiana suaveolens defensin 7; PA, phosphatidic acid; PC3, human prostate adenocarcinoma; PEG 400, polyethylene glycol 400; PI, propidium iodide; PIP2, phosphatidylinositol 4,5-bisphosphate; RBC, red blood cell; r.m.s.d., random mean SD; RsAFP, Raphanus sativus antifungal protein; TPP3, tomato pistil predominant defensin 3; U937, human myelomonocytic antimicrobial and anticancer activity of these HDPs has largely been attributed to their ability to bind and destabilize cell membranes. Such HDPs are attracting significant interest as potential novel antibiotics and as alternatives to conventional cancer chemotherapy based on their selectivity and proposed lower likelihood to generate acquired resistance (3,(5)(6)(7).…”

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confidence: 99%

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Structural and functional characterization of the membrane‐permeabilizing activity of Nicotiana occidentalis defensin NoD173 and protein engineering to enhance oncolysis

et al. 2019

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Defensins are an extensive family of host defense peptides found ubiquitously across plant and animal species. In addition to protecting against infection by pathogenic microorganisms, some defensins are selectively cytotoxic toward tumor cells. As such, defensins have attracted interest as potential antimicrobial and anticancer therapeutics. The mechanism of defensin action against microbes and tumor cells appears to be conserved and involves the targeting and disruption of cellular membranes. This has been best defined for plant defensins, which upon binding specific phospholipids, such as phosphatidylinositol 4,5‐bisphosphate (PIP2) and phosphatidic acid, form defensin‐lipid oligomeric complexes that destabilize membranes, leading to cell lysis. In this study, to further define the anticancer and therapeutic properties of plant defensins, we have characterized a novel plant defensin, Nicotiana occidentalis defensin 173 (NoD173), from N. occidentalis. NoD173 at low micromolar concentrations selectively killed a panel of tumor cell lines over normal primary cells. To improve the anticancer activity of NoD173, we explored increasing cationicity by mutation, with NoD173 with the substitution of Q22 with lysine [NoD173 (Q22K)], increasing the antitumor cell activity by 2‐fold. NoD173 and the NoD173(Q22K) mutant exhibited only low levels of hemolytic activity, and both maintained activity against tumor cells in serum. The ability of NoD173 to inhibit solid tumor growth in vivo was tested in a mouse B16‐F1 model, whereby injection of NoD173 into established subcutaneous tumors significantly inhibited tumor growth. Finally, we showed that NoD173 specifically targets PIP2 and determined by X‐ray crystallography that a high‐resolution structure of NoD173, which forms a conserved family‐defining cysteine‐stabilized–αβ motif with a dimeric lipid‐binding conformation, configured into an arch‐shaped oligomer of 4 dimers. These data provide insights into the mechanism of how defensins target membranes to kill tumor cells and provide proof of concept that defensins are able to inhibit tumor growth in vivo.—Lay, F. T., Ryan, G. F., Caria, S., Phan, T. K., Veneer, P. K., White, J. A., Kvansakul, M., Hulett M. D. Structural and functional characterization of the membrane‐permeabilizing activity of Nicotiana occidentalis defensin NoD173 and protein engineering to enhance oncolysis. FASEB J. 33, 6470–6482 (2019). http://www.fasebj.org

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confidence: 99%

Structural and functional characterization of the membrane‐permeabilizing activity of Nicotiana occidentalis defensin NoD173 and protein engineering to enhance oncolysis

et al. 2019

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“…Therefore, high selectivity and specificity to cancer cells are the most desired properties of novel anti-cancer chemotherapeutic drugs [ 44 , 45 ]. CAPs have attracted significant interest and have been proposed as a novel family of anticancer molecules over the past decade [ 46 , 47 ]. CAPs are small, amphipathic, and positively charged peptides present in all forms of life and comprise a major component of the innate immune system against various microbial pathogens [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Cationic antimicrobial peptide NRC-03 induces oral squamous cell carcinoma cell apoptosis via CypD-mPTP axis-mediated mitochondrial oxidative stress

Hou

Mao

et al. 2022

Redox Biology

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“…Although ABPs are introduced vertically into the lipid membrane, no peptide-peptide interaction is created (Wimley, 2010). In this arrangement the helical hydrophilic head is positioned toward the hydrophilic portion of lipids, the aqueous phase is outside the membrane and the hydrophobic head is positioned in the membrane's hydrophobic center (Gaspar and Castanho, 2016). In the toroidal model, the arrangement of hydrophilic and hydrophobic regions in the bilayer membrane is changed and damaged.…”

Section: Carpet Modelmentioning

confidence: 99%

Exploring the biogenic peptide’s potential in combating bacterial zoonosis: application and future prospect – a review

Tahir

Abbas

Qamar

et al. 2024

Annals of Animal Science

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Worldwide, microbial infections have a serious impact because they cause infectious diseases, death, and significant economic losses. Zoonosis is now a major public health issue on a global scale because of the fast expansion of human exploitation of nature and animal husbandry. Notably, in the past 30 years, over 30 novel human infections have been discovered, 75% of which fall under the category of zoonosis. Resistant strains have emerged as a result of improper use of antibiotics and insufficient infection management posing a serious risk to both public health and the global economy. As alternatives, antimicrobial peptides are showing good results. The majority of living things use antibacterial peptides (ABPs) as a key part of their natural defenses against invading infections. These peptides are cationic, amphipathic, and relatively tiny with varied sequences, structures, and lengths. For the delivery of these efficacious biological peptides, nanoparticles are providing opportunities for effective, safe, and viable delivery. An innovative method of treating infectious diseases is demonstrated by nanoparticles and antibacterial peptides. When ABPs are combined with carrier nanoparticles to optimize distribution, their half-life may be increased, allowing for lower dosages and ultimately lower toxicity. For biological applications, ABPs and nanoparticle conjugates have become effective methods, enabling the treatment, prevention of disease, and detection. More than 50 peptide medications have been made available for purchase on the market as of 2018. Around 25 billion USD is spent on peptide medications each year, including ABPs. But still, there is a gap in the distribution of these ABPs as an alternative to synthetic antibiotics. It might be due to the high cost of these goods. Thus, scientists, researchers, and commercializing companies should work together so that these ABPs with a safe delivery system should be available in the market to combat resistant strains of bacteria. In doing so, we draw attention to the significant advancements made in the field as well as the difficulties still encountered in developing imaging species, active therapies, and nano-drug delivery systems that are functionalized with peptides and proteins for clinical use.

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Anticancer Peptides: Prospective Innovation in Cancer Therapy

Cited by 9 publications

References 87 publications

Structural and functional characterization of the membrane‐permeabilizing activity of Nicotiana occidentalis defensin NoD173 and protein engineering to enhance oncolysis

Structural and functional characterization of the membrane‐permeabilizing activity of Nicotiana occidentalis defensin NoD173 and protein engineering to enhance oncolysis

Cationic antimicrobial peptide NRC-03 induces oral squamous cell carcinoma cell apoptosis via CypD-mPTP axis-mediated mitochondrial oxidative stress

Exploring the biogenic peptide’s potential in combating bacterial zoonosis: application and future prospect – a review

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