Mechanism of Anticancer Effects of Antimicrobial Peptides

Li, Xuan; Li, Yang; Li, Zhi; Lan, Xiujin; Leung, Polly H.M.; Li, Jiashen; Yang, Mo; Ko, Frank; Qin, Ling

doi:10.3993/jfbi03201503

Cited by 30 publications

(28 citation statements)

References 78 publications

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“…This is in agreement with the reported IC 50 values of the plant defensins NaD1, sesquin and limenin [24][25][26]. Additionally, PaDef defensin was not cytotoxic to peripheral blood mononuclear cells, suggesting that the peptide could be selective to cancer cells; however, further experiments are required to demonstrate it.…”

Section: Discussionsupporting

confidence: 92%

The defensin from avocado (Persea americana var. drymifolia) PaDef induces apoptosis in the human breast cancer cell line MCF-7

Guzmán-Rodríguez

López-Gómez

Salgado‐Garciglia

et al. 2016

Biomedicine & Pharmacotherapy

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Section: Discussionsupporting

confidence: 92%

The defensin from avocado (Persea americana var. drymifolia) PaDef induces apoptosis in the human breast cancer cell line MCF-7

Guzmán-Rodríguez

López-Gómez

Salgado‐Garciglia

et al. 2016

Biomedicine & Pharmacotherapy

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“…As major examples, lactoferrin and its derivatives have been extensively investigated as potential drugs for the treatment of common viral infections including the common cold, influenza, viral gastroenteritis and herpes [275] whilst the inhibitory effects of these proteins and peptides against the proliferation of multiple cancers, has suggested a potential role in cancer prevention [276]. It is well established that many AMPs and antimicrobial proteins have anticancer activity that generally appears to involve mechanisms of membranolysis that are similar to those used by these molecules in their action against microbes [277,278], which in some cases shows pH dependence [98], as recently described [279,280]. Advanced clinical trials have shown that the administration of lactoferrin has no significant side effects and that the protein has efficacy in treating iron deficiency anemia in pregnant women [281], sepsis in premature neonates, which is a common and severe complication in new-born infants [282] and infections due to Helicobacter pylori , which is causally associated with gastritis and peptic ulcer diseases [283].…”

Section: Potential Applications Of Ph Dependent Antimicrobial Peptmentioning

confidence: 99%

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

et al. 2016

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Antimicrobial peptides (AMPs) are potent antibiotics of the innate immune system that have been extensively investigated as a potential solution to the global problem of infectious diseases caused by pathogenic microbes. A group of AMPs that are increasingly being reported are those that utilise pH dependent antimicrobial mechanisms, and here we review research into this area. This review shows that these antimicrobial molecules are produced by a diverse spectrum of creatures, including vertebrates and invertebrates, and are primarily cationic, although a number of anionic examples are known. Some of these molecules exhibit high pH optima for their antimicrobial activity but in most cases, these AMPs show activity against microbes that present low pH optima, which reflects the acidic pH generally found at their sites of action, particularly the skin. The modes of action used by these molecules are based on a number of major structure/function relationships, which include metal ion binding, changes to net charge and conformational plasticity, and primarily involve the protonation of histidine, aspartic acid and glutamic acid residues at low pH. The pH dependent activity of pore forming antimicrobial proteins involves mechanisms that generally differ fundamentally to those used by pH dependent AMPs, which can be described by the carpet, toroidal pore and barrel-stave pore models of membrane interaction. A number of pH dependent AMPs and antimicrobial proteins have been developed for medical purposes and have successfully completed clinical trials, including kappacins, LL-37, histatins and lactoferrin, along with a number of their derivatives. Major examples of the therapeutic application of these antimicrobial molecules include wound healing as well as the treatment of multiple cancers and infections due to viruses, bacteria and fungi. In general, these applications involve topical administration, such as the use of mouth washes, cream formulations and hydrogel delivery systems. Nonetheless, many pH dependent AMPs and antimicrobial proteins have yet to be fully characterized and these molecules, as a whole, represent an untapped source of novel biologically active agents that could aid fulfillment of the urgent need for alternatives to conventional antibiotics, helping to avert a return to the pre-antibiotic era.

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“…Although AMPs are primarily known for their antimicrobial properties, some examples and their derivatives are reported as potent antitumor agents with low toxicity such as temporin-1CEa, ascaphin-8, alyteserin-2 and magainin-2 [13][14][15][16][17]. These AMPs bind to the plasma membrane and cause cell death by either necrosis or apoptosis [18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of breast cancer targeting conjugate of temporin-SHa analog and its effect on pro- and anti-apoptotic protein expression in MCF-7 cells

et al. 2018

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The frog natural product temporin-SHa (FLSGIVGMLGKLF) is a potent antimicrobial peptide, as is the analog [S3K]SHa. By solid-phase synthesis, we prepared temporin-SHa and several temporin-SHa analogs with one or more D-alanine residues incorporated. The natural product and the analog [G10a]SHa were found to be cytotoxic in mammalian cell lines and induce cell death. To achieve selectivity, we conjugated the analog [G10a]SHa with a breast cancer targeting peptide (BCTP). The resulting peptide temporin [G10a]SHa-BCTP conjugate was selectively active against the MCF-7 breast cancer cell line with no cytotoxicity in NIH-3T3 fibroblasts. Unlike the natural product or [G10a]SHa, the conjugated peptide induced apoptosis, downregulating the expression of Bcl-2 and survivin and upregulating Bax and caspase-3.

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Mechanism of Anticancer Effects of Antimicrobial Peptides

Cited by 30 publications

References 78 publications

The defensin from avocado (Persea americana var. drymifolia) PaDef induces apoptosis in the human breast cancer cell line MCF-7

The defensin from avocado (Persea americana var. drymifolia) PaDef induces apoptosis in the human breast cancer cell line MCF-7

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

Synthesis of breast cancer targeting conjugate of temporin-SHa analog and its effect on pro- and anti-apoptotic protein expression in MCF-7 cells

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