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
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DOI：
10.1186/s12906-019-2528-2
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发表时间：
2019-06-03
影响因子：
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通讯作者：
Yusoff, Khatijah
中科院分区：
文献类型：
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作者：
Chuah, Li-Oon;Foo, Hooi Ling;Yusoff, Khatijah
植物乳杆菌是乳酸菌(LAB)的主要种类之一，能够产生具有显著益生作用的后生代谢产物(PM)，已被广泛报道用于大鼠、家禽和猪。尽管有新的证据表明LAB具有抗癌活性，但有关植物乳杆菌产生的PM的细胞毒性和抗增殖活性的信息却非常有限。方法采用四甲基偶氮唑蓝比色法、台盼蓝拒染法和BrdU比色法测定了6株植物乳杆菌产生的代谢产物(PM)对正常人原代细胞、乳腺癌细胞、结直肠癌细胞、宫颈癌细胞、肝癌细胞和白血病细胞的抑制作用和细胞毒作用。用溶血法测定了PM对人和各种动物红细胞的毒性。结果筛选出的UL4 PM对MCF-7、RG14 PMon HT29、RG11和RI11 PMon HL60的IC50值最低。对人、狗、兔和鸡的红细胞均无溶血作用，对正常乳腺MCF-10A细胞及原代培养的人外周血单核细胞、小鼠脾细胞和胸腺细胞均无细胞毒性。30%(v/v)的UL4和RG 14 PM作用72小时后，分别能有效地诱导MCF-7和HT-29细胞的增殖抑制。荧光显微镜观察和流式细胞仪分析表明，UL4 PM对MCF-7细胞具有明显的细胞毒作用。结论6株植物乳杆菌产生的PM具有选择性细胞毒作用，其抗肿瘤细胞增殖和诱导细胞凋亡的作用具有菌株特异性和癌细胞类型特异性，而对正常细胞无明显影响。这揭示了植物乳杆菌PM作为功能补充剂和癌症辅助治疗的巨大潜力。
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 PMon HT29 and RG11 and RI11 PMon 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 14PM respectively after 72h 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.