Nisin ZP, a Bacteriocin and Food Preservative, Inhibits Head and Neck Cancer Tumorigenesis and Prolongs Survival

Kamarajan, Pachiyappan; Hayami, Takayuki; Matte, Bibiana Franzen; Liu, Yang; Danciu, Theodora E.; Ramamoorthy, Ayyalusamy; Worden, Francis P.; Kapila, Sunil; Kapila, Yvonne L.

doi:10.1371/journal.pone.0131008

Cited by 165 publications

(131 citation statements)

References 57 publications

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“…This result is in accordance with previous studies on HaCaT cells, however, performed with Nisin Z . Our result contradicts findings from a previous study, where Nisin A was cytotoxic against HUVEC where 50% of the cells died at 100 μg/ml …”

Section: Discussionsupporting

confidence: 89%

Immunomodulatory potential of Nisin A with application in wound healing

Mouritzen

Andrea

Qvist

et al. 2019

Wound Repair Regeneration

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Antimicrobial peptides can have a dual role with both antimicrobial activity against a broad range of bacteria and immunomodulatory effect, making them attractive as therapeutic treatment of difficult wounds. Nisin A is widely known for its antimicrobial activity, and a preliminary study demonstrated that it increased wound closure, but the mechanism behind its effect is unknown. The aim of this study is to elucidate the wound healing potential of Nisin A and the mechanism behind. First, an epithelial and endothelial cell line, human keratinocyte (HaCaT) and human umbilical vein endothelial cell, were used to demonstrate migration and proliferation effects in vitro. From HaCaT cells and peripheral blood mononuclear cell, changes in cytokine levels were shown by quantitative polymerase chain reaction and enzyme‐linked immunosorbent assay. Second, the ex vivo porcine wound healing model was used to investigate the re‐epithelization potential of Nisin A. Finally, the model Galleria mellonella was used to confirm antimicrobial activity and to investigate potential immunomodulatory effects in vivo. Here, we demonstrated that Nisin A affected migration significantly of both human umbilical vein endothelial cell and HaCaT cells (p < 0.05) but not proliferation, potentially by decreasing the levels of proinflammatory cytokines tumor necrosis factor‐α, interleukin‐6, and interleukin‐8 (p < 0.001). Furthermore, Nisin A treatment diminished lipopolysaccharide‐induced tumor necrosis factor‐α levels from peripheral blood mononuclear cells and monocyte chemoattractant protein‐1 from HaCaT cells (p < 0.001). Furthermore, Nisin A did not affect proliferation ex vivo either but increased re‐epithelization of the porcine skin. Nisin A improved survival of G. mellonella significantly from Staphylococcus epidermidis (p < 0.001) but not from Escherichia coli, indicating that Nisin A did not help the larvae to survive the infection in a different than direct antimicrobial way. All together this makes Nisin A a potential treatment to use in wound healing, as it increases the mobility of skin cells, dampens the effect of lipopolysaccharide and proinflammatory cytokines, and decreases bacterial growth.

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Section: Discussionsupporting

confidence: 89%

Immunomodulatory potential of Nisin A with application in wound healing

Mouritzen

Andrea

Qvist

et al. 2019

Wound Repair Regeneration

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“…; Kamarajan et al . ). For example, nisin has beneficial properties in the context of biomedical applications, including bacterial infections, cancer, oral diseases and more.…”

Section: Nisin: a Bacterially Derived Antimicrobialmentioning

confidence: 97%

“…) (Kamarajan et al . ). Considering that the FDA has approved 83·25 mg kg −1 in humans as the no‐observed‐effect‐level for nisin (66·7 mg kg −1 was used in mice as a cancer therapeutic dose), this study demonstrated the promising potential for nisin as an anticancer agent.…”

Section: Bacteriocins and Cancer: Nisin As A Cancer Therapeuticmentioning

confidence: 97%

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Biomedical applications of nisin

et al. 2016

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Nisin is a bacteriocin produced by a group of Gram-positive bacteria that belongs to Lactococcus and Streptococcus species. Nisin is classified as a Type A (I) lantibiotic that is synthesized from mRNA and the translated peptide contains several unusual amino acids due to post-translational modifications. Over the past few decades, nisin has been used widely as a food biopreservative. Since then, many natural and genetically modified variants of nisin have been identified and studied for their unique antimicrobial properties. Nisin is an FDA approved and GRAS (generally regarded as safe) peptide with recognized potential for clinical use. Over the past two decades the application of nisin has been extended to biomedical fields. Studies have reported that nisin can prevent the growth of drug-resistant bacterial strains, such as methicillin resistant Staphylococcus aureus, Streptococcus pneumoniae, Enterococci and Clostridium difficile. Nisin has now been shown to have antimicrobial activity against both Gram-positive and Gram-negative disease-associated pathogens. Nisin has been reported to have anti-biofilm properties and can work synergistically in combination with conventional therapeutic drugs. In addition, like host defense peptides, nisin may activate the adaptive immune response and have an immunomodulatory role. Increasing evidence indicates that nisin can influence the growth of tumors and exhibit selective cytotoxicity towards cancer cells. Collectively, the application of nisin has advanced beyond its role as a food biopreservative. Thus, this review will describe and compare studies on nisin and provide insight into its future biomedical applications.

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“…In addition, with demonstrated safety over the past 40 years, the use of nisin has expanded into a diverse array of applications, including those related to the biomedical industry . Many lantibiotics possess additional biological activities beyond their antimicrobial activities . Therefore, nisin has beneficial properties in the context of biomedical applications, including bacterial infections, cancer, immune modulation, oral diseases, and more.…”

Section: A Unique Probiotic Nisin‐producing Lactococcus Lactismentioning

confidence: 99%

Probiotics, including nisin‐based probiotics, improve clinical and microbial outcomes relevant to oral and systemic diseases

Nguyen

Brody

Lin

et al. 2019

Periodontology 2000

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The effects of probiotic supplementation on systemic health and gastrointestinal diseases have been investigated in numerous studies. The aim of this review is to provide an overview of probiotics and their effects on periodontal health. Probiotics show beneficial effects as adjunctive therapeutics and as stand‐alone agents in the treatment and prevention of gingivitis as well as specific clinical parameters of periodontitis. This review focuses on the clinical and microbiological aspects of probiotics in the context of health, gingivitis, and periodontitis. In addition, a special focus on nisin‐producing probiotics and nisin itself showcase their significant potential for oral and systemic use.

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Nisin ZP, a Bacteriocin and Food Preservative, Inhibits Head and Neck Cancer Tumorigenesis and Prolongs Survival

Cited by 165 publications

References 57 publications

Immunomodulatory potential of Nisin A with application in wound healing

Immunomodulatory potential of Nisin A with application in wound healing

Biomedical applications of nisin

Probiotics, including nisin‐based probiotics, improve clinical and microbial outcomes relevant to oral and systemic diseases

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