Assuring consumer safety without animals

Westmoreland, Carl; Holmes, Anthony

doi:10.4161/org.5.2.9128

Cited by 14 publications

(6 citation statements)

References 28 publications

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“…Assessment of potential risk to human health is essential for the products including those for food, home care, personal care, pharmaceutical use and pesticides [51]. Most cytotoxic agents are not only targeting to the rapidly dividing cancer cells, but also simultaneously giving deleterious side effect to some rapidly dividing normal cells.…”

Section: Discussionmentioning

confidence: 99%

Postbiotic metabolites produced by Lactobacillus plantarum strains exert selective cytotoxicity effects on cancer cells

Chuah

Foo

Loh

et al. 2019

BMC Complement Altern Med

143

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Background Lactobacillus plantarum , a major species of Lactic Acid Bacteria (LAB), are capable of producing postbiotic metabolites (PM) with prominent probiotic effects that have been documented extensively for rats, poultry and pigs. Despite the emerging evidence of anticancer properties of LAB, very limited information is available on cytotoxic and antiproliferative activity of PM produced by L. plantarum . Therefore, the cytotoxicity of PM produced by six strains of L. plantarum on various cancer and normal cells are yet to be evaluated. Methods Postbiotic metabolites (PM) produced by six strains of L. plantarum were determined for their antiproliferative and cytotoxic effects on normal human primary cells, breast, colorectal, cervical, liver and leukemia cancer cell lines via MTT assay, trypan blue exclusion method and BrdU assay. The toxicity of PM was determined for human and various animal red blood cells via haemolytic assay. The cytotoxicity mode was subsequently determined for selected UL4 PM on MCF-7 cells due to its pronounced cytotoxic effect by fluorescent microscopic observation using AO/PI dye reagents and flow cytometric analyses. Results UL4 PM exhibited the lowest IC 50 value on MCF-7, RG14 PM on HT29 and RG11 and RI11 PM on HL60 cell lines, respectively from MTT assay. Moreover, all tested PM did not cause haemolysis of human, dog, rabbit and chicken red blood cells and demonstrated no cytotoxicity on normal breast MCF-10A cells and primary cultured cells including human peripheral blood mononuclear cells, mice splenocytes and thymocytes. Antiproliferation of MCF-7 and HT-29 cells was potently induced by UL4 and RG 14 PM respectively after 72 h of incubation at the concentration of 30% (v/v). Fluorescent microscopic observation and flow cytometric analyses showed that the pronounced cytotoxic effect of UL4 PM on MCF-7 cells was mediated through apoptosis. Conclusion In conclusion , PM produced by the six strains of L. plantarum exhibited selective cytotoxic via antiproliferative effect and induction of apoptosis against malignant cancer cells in a strain-specific and cancer cell type-specific manner whilst sparing the normal cells. This reveals the vast potentials of PM from L. plantarum as functional supplement and as an adjunctive treatment for cancer.

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Section: Discussionmentioning

confidence: 99%

Postbiotic metabolites produced by Lactobacillus plantarum strains exert selective cytotoxicity effects on cancer cells

Chuah

Foo

Loh

et al. 2019

BMC Complement Altern Med

143

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“…Moreover, it is often difficult to test these new drugs using human antibodies in mouse models due to lack of cross-reactivity with the murine target. Testing such antibody candidates in three-dimensional human tissue models allows predictions of the safety of several candidate molecules long before preclinical testing in non-human primates or in human clinical situations [29] . Until recently, experimental paradigms have been based primarily on two-dimensional, monolayer culture systems.…”

Section: Discussionmentioning

confidence: 99%

Integrin-Blocking Antibodies Delay Keratinocyte Re-Epithelialization in a Human Three-Dimensional Wound Healing Model

et al. 2010

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The α6β4 integrin plays a significant role in tumor growth, angiogenesis and metastasis through modulation of growth factor signaling, and is a potentially important therapeutic target. However, α6β4-mediated cell-matrix adhesion is critical in normal keratinocyte attachment, signaling and anchorage to the basement membrane through its interaction with laminin-5, raising potential risks for targeted therapy. Bioengineered Human Skin Equivalent (HSE), which have been shown to mimic their normal and wounded counterparts, have been used here to investigate the consequences of targeting β4 to establish toxic effects on normal tissue homeostasis and epithelial wound repair. We tested two antibodies directed to different β4 epitopes, one adhesion-blocking (ASC-8) and one non-adhesion blocking (ASC-3), and determined that these antibodies were appropriately localized to the basal surface of keratinocytes at the basement membrane interface where β4 is expressed. While normal tissue architecture was not altered, ASC-8 induced a sub-basal split at the basement membrane in non-wounded tissue. In addition, wound closure was significantly inhibited by ASC-8, but not by ASC-3, as the epithelial tongue only covered 40 percent of the wound area at 120 hours post-wounding. These results demonstrate β4 adhesion-blocking antibodies may have adverse effects on normal tissue, whereas antibodies directed to other epitopes may provide safer alternatives for therapy. Taken together, we conclude that these three-dimensional tissue models provide a biologically relevant platform to identify toxic effects induced by candidate therapeutics, which will allow generation of findings that are more predictive of in vivo responses early in the drug development process.

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“…This provides the biological context and supporting weight of evidence to facilitate the interpretation of such alternative data [3]. Severe eye irritants and substances that could cause allergic contact dermatitis is the only option where major progress has been made in reducing and replacing animal use [4]. For other hazards that can cause cancer or birth defects, development of in vitro tests that reliably identify hazards is more difficult because of the number of different mechanisms involved in these complex biological processes.…”

Section: Alternatives In Cancer Researchmentioning

confidence: 99%

Alternatives and Refinement for Animal Experimentation in Cancer Research

Ingle

2018

Alternatives to Animal Testing

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Globally cancer is a major public health issue and is a second biggest cause of deaths. Although animal models have limitations in terms of predictive and translational value to humans, they have played a major role in understanding this disease and anticancer drug discovery. In cancer research the most commonly used animal species are mice, rats, hamsters, rabbits, Guinea pigs, fish and amphibians. Use of different cell lines in tissue culture system offers a great relief from use of animals at the same time provide important clues before embarking the animal experiments. Use of spontaneously developing tumor models are encouraged rather producing diseases in the animals. Beside the alternatives, refinement also plays important role in reducing the animal usage in cancer research. However, cancer research use whole body system to evaluate the new strategies for diagnosis and treatment of cancer. This paper highlights the available alternatives and refinements for animal experimentation. A positive note is that if coupled with the refinements, even a minimised number of animal usage shall also yield the meaningful and acceptable results.

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Assuring consumer safety without animals

Cited by 14 publications

References 28 publications

Postbiotic metabolites produced by Lactobacillus plantarum strains exert selective cytotoxicity effects on cancer cells

Postbiotic metabolites produced by Lactobacillus plantarum strains exert selective cytotoxicity effects on cancer cells

Integrin-Blocking Antibodies Delay Keratinocyte Re-Epithelialization in a Human Three-Dimensional Wound Healing Model

Alternatives and Refinement for Animal Experimentation in Cancer Research

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