A lysate of a multi-strain probiotic formulation inhibits cell growth and oxidative phosphorylation in colorectal cancer cells via a ceramide-mediated mechanism.

IF 3.5 4区 医学 Q2 MICROBIOLOGY
D Gnocchi, F Lombardi, B Cinque, R R Paparella, P Palumbo, A Mazzocca
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引用次数: 0

Abstract

The multi-strain probiotic formulation (MPF - Oxxyslab™) regulates several biological processes, including oxygenation in human and mouse models of neurodegenerative diseases. Its effect on oxidative metabolism of tumour cells has not yet been investigated. Employing a polarographic approach, we examined the effect of a lysate of MPF and its constituent strains on oxidative phosphorylation (OXPHOS) in colorectal cancer cells. Results indicate that MPF lysate selectively inhibits OXPHOS in undifferentiated but not in differentiated Caco-2 cells. Ceramides, produced through bacterial sphingomyelinase activity, mediate the inhibitory effects of MPF lysate, and the efficacy of the lysate of individual MPF strains in blocking cellular respiration varies due to strain-specific differences in ceramide production. Our results demonstrate that MPF lysate exhibits anti-OXPHOS activity in human colorectal carcinoma cells, selectively targeting undifferentiated Caco-2 cells but not differentiated ones. The reliance of colorectal cancer cells on OXPHOS provides a scientific basis for exploring MPF probiotic formulation as a complementary approach to conventional pharmacology.

多菌株益生菌制剂的裂解物通过神经酰胺介导的机制抑制结直肠癌细胞的细胞生长和氧化磷酸化。
多菌株益生菌制剂(MPF - Oxxyslab™)调节多种生物过程,包括人类和小鼠神经退行性疾病模型中的氧合。其对肿瘤细胞氧化代谢的影响尚未被研究。采用极谱法,我们研究了MPF裂解物及其组成菌株对结直肠癌细胞氧化磷酸化(OXPHOS)的影响。结果表明,MPF裂解液对未分化的Caco-2细胞有选择性抑制OXPHOS,而对已分化的Caco-2细胞无选择性抑制作用。神经酰胺通过细菌鞘磷脂酶活性产生,介导MPF裂解物的抑制作用,而单个MPF菌株裂解物阻断细胞呼吸的效果因菌株特异性神经酰胺产生的差异而异。我们的研究结果表明,MPF裂解物在人结直肠癌细胞中具有抗oxphos活性,选择性地靶向未分化的Caco-2细胞,而不是分化的Caco-2细胞。结直肠癌细胞对OXPHOS的依赖为探索MPF益生菌制剂作为传统药理学的补充方法提供了科学依据。
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来源期刊
Beneficial microbes
Beneficial microbes MICROBIOLOGY-NUTRITION & DIETETICS
CiteScore
7.90
自引率
1.90%
发文量
53
审稿时长
>12 weeks
期刊介绍: Beneficial Microbes is a peer-reviewed scientific journal with a specific area of focus: the promotion of the science of microbes beneficial to the health and wellbeing of man and animal. The journal contains original research papers and critical reviews in all areas dealing with beneficial microbes in both the small and large intestine, together with opinions, a calendar of forthcoming beneficial microbes-related events and book reviews. The journal takes a multidisciplinary approach and focuses on a broad spectrum of issues, including safety aspects of pro- & prebiotics, regulatory aspects, mechanisms of action, health benefits for the host, optimal production processes, screening methods, (meta)genomics, proteomics and metabolomics, host and bacterial physiology, application, and role in health and disease in man and animal. Beneficial Microbes is intended to serve the needs of researchers and professionals from the scientific community and industry, as well as those of policy makers and regulators. The journal will have five major sections: * Food, nutrition and health * Animal nutrition * Processing and application * Regulatory & safety aspects * Medical & health applications In these sections, topics dealt with by Beneficial Microbes include: * Worldwide safety and regulatory issues * Human and animal nutrition and health effects * Latest discoveries in mechanistic studies and screening methods to unravel mode of action * Host physiology related to allergy, inflammation, obesity, etc. * Trends in application of (meta)genomics, proteomics and metabolomics * New developments in how processing optimizes pro- & prebiotics for application * Bacterial physiology related to health benefits
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