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从人乳中分离的益生菌干酪乳杆菌和副干酪乳杆菌菌株对宫颈癌(HeLa)细胞系的抗癌潜力。

Anticancer potential against cervix cancer (HeLa) cell line of probiotic Lactobacillus casei and Lactobacillus paracasei strains isolated from human breast milk.

机构信息

Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, Shaanxi, People's Republic of China.

出版信息

Food Funct. 2018 May 23;9(5):2705-2715. doi: 10.1039/c8fo00547h.

Abstract

Lactic acid bacteria have been categorized as probiotics and play a crucial role in human health by stimulating the supply of nutrients, shaping the immune system, and preventing the colonization of pathogenic microbes. This study investigated the mechanisms for the action of three potential probiotic Lactobacillus strains: Lactobacillus casei SR1, Lactobacillus casei SR2, and Lactobacillus paracasei SR4 isolated from human breast milk. These Lactobacillus strains were identified via 16S DNA sequencing and characterized via biochemical assays including acid resistance, bile resistance, antioxidant activity, and antibiotic susceptibility. The bioactivity of the cell-free culture supernatant (CFCS) secreted by these strains on the cervix cancer (HeLa) cell line was also evaluated via cytotoxicity assay and apoptosis analysis. The mechanism of anticancer activity was also investigated via RT-qPCR and western blotting. The results demonstrated that these newly isolated Lactobacillus strains from human milk displayed noticeable probiotic characteristics such as excellent antibiotic susceptibility, outstanding antioxidant activity, and promising resistance to low pH and high concentration of bile salts. The results of the conducted bioactivity assays verified that the CFCSs had acceptable anticancer effects on cervix cancer (HeLa) cells by upregulating the expression of apoptotic genes BAX, BAD, caspase3, caspase8, and caspase9 and by downregulating the expression of the BCl-2 gene. Overall, these results indicate that the Lactobacillus strains isolated from human breast milk could be considered as a topical medication with a potential therapeutic index due to their efficacy against cervix cancer cells.

摘要

乳酸菌已被归类为益生菌,通过刺激营养供应、塑造免疫系统和防止病原微生物定植,在人类健康中发挥着关键作用。本研究调查了三种潜在益生菌乳杆菌菌株的作用机制:从人乳中分离出的 Lactobacillus casei SR1、Lactobacillus casei SR2 和 Lactobacillus paracasei SR4。这些乳杆菌菌株通过 16S DNA 测序进行鉴定,并通过生化测定进行特征分析,包括耐酸性、耐胆盐性、抗氧化活性和抗生素敏感性。还通过细胞毒性测定和细胞凋亡分析评估了这些菌株分泌的无细胞培养上清液(CFCS)对宫颈癌细胞(HeLa)系的生物活性。还通过 RT-qPCR 和 Western blot 研究了抗癌活性的机制。结果表明,这些从人乳中分离出的新型乳杆菌菌株表现出显著的益生菌特性,如良好的抗生素敏感性、出色的抗氧化活性以及对低 pH 值和高浓度胆盐的良好耐受性。进行的生物活性测定结果证实,CFCS 通过上调凋亡基因 BAX、BAD、caspase3、caspase8 和 caspase9 的表达,并下调 BCl-2 基因的表达,对宫颈癌细胞(HeLa)具有可接受的抗癌作用。总的来说,这些结果表明,从人乳中分离出的乳杆菌菌株由于对宫颈癌细胞的疗效,可被视为具有潜在治疗指数的局部用药。

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