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

Li-Oon Chuah,Khatijah Yusoff,Raha Abdul Rahim,Hooi Ling Foo,Noorjahan Banu Mohammed Alitheen,Swee Keong Yeap,Teck Chwen Loh,Nur Elina Abdul Mutalib

doi:10.1186/s12906-019-2528-2

Li-Oon Chuah, Khatijah Yusoff + Show 6 more

Open Access

https://doi.org/10.1186/s12906-019-2528-2

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Abstract

BackgroundLactobacillus 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.MethodsPostbiotic 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.ResultsUL4 PM exhibited the lowest IC50 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.ConclusionIn 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.

Highlights

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
Bacterial cultures Six bacteriocin-producing L. plantarum identified as IUL4, TL1, RS5, RI11, RG11 and RG14 strains [43] were isolated from Malaysian foods [44] and obtained from the Laboratory of Industrial Biotechnology, Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia (UPM)
Cytotoxic effect of PM on various cancer and normal cells The inhibition concentration of 50% growth (IC50) were determined for various cancer cell lines to compare the cytotoxicity effects of PM produced by L. plantarum IUL4, TL1, RS5, RG14, RG11 and RI11, which was designated as UL4 PM, TL1 PM, RS5 PM, RG14 PM, RG11 PM and RI11 PM, respectively

Summary

Introduction

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. Numerous in vivo, in vitro, human and epidemiological studies have provided increasing evidence of LAB effects on colon, bladder, liver, breast, and gastric cancers [8,9,10,11,12]. These effects are mediated by various mechanisms, such as the alteration of gastrointestinal microflora, enhancement of the host’s immune response, antioxidative, antiproliferative, and induction of apoptosis [13, 14]. Antibiotic resistance is a major safety concern when the resistance is transferrable, especially to pathogenic bacteria [20] Another concern for the application of living probiotic cultures is their viability below expected standards. Several clinical studies demonstrated the use of live bacteria might possess adverse effects such as acute inflammation and increased mortality [23, 24]

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