关键词: Carcinogenesis Colorectal cancer K2-MK7 Microbiome Vitamin K2

来  源:   DOI:10.1186/s12935-023-03114-2   PDF(Pubmed)

Abstract:
Colorectal cancer (CRC) is one of the foremost causes of cancer-related deaths. Lately, a close connection between the course of CRC and the intestinal microbiota has been revealed. Vitamin K2 (VK2) is a bacterially derived compound that plays a crucial role in the human body. Its significant anti-cancer properties may result, inter alia, from a quinone ring possessing a specific chemical structure found in many chemotherapeutics. VK2 can be supplied to our body exogenously, i.e., through dietary supplements or fermented food (e.g., yellow cheese, fermented soybeans -Natto), and endogenously, i.e., through the production of bacteria that constantly colonize the human microbiome of the large intestine.This paper focuses on endogenous K2 synthesized by the most active members of the human gut microbiome. This analysis tested 86 intestinally derived bacterial strains, among which the largest VK2 producers (Lactobacillus, Bifidobacterium, Bacillus) were selected. Moreover, based on the chosen VK2-MK4 homolog, the potential of VK2 penetration into Caco-2 cells in an aqueous environment without the coexistence of fats, pancreatic enzymes, or bile salts has been displayed. The influence of three VK2 homologs: VK2-MK4, VK2-MK7 and VK2-MK9 on apoptosis and necrosis of Caco-2 cells was tested proving the lack of their harmful effects on the tested cells. Moreover, the unique role of long-chain homologs (VK2-MK9 and VK2-MK7) in inhibiting the secretion of pro-inflammatory cytokines such as IL-8 (for Caco-2 tissue) and IL-6 and TNFα (for RAW 264.7) has been documented.
摘要:
结直肠癌(CRC)是癌症相关死亡的首要原因之一。最近,已经揭示了CRC病程与肠道微生物群之间的密切联系.维生素K2(VK2)是一种细菌衍生的化合物,在人体中起着至关重要的作用。其显著的抗癌特性可能会导致,除其他外,从具有在许多化学治疗剂中发现的特定化学结构的醌环。VK2可以外源供应给我们的身体,即,通过膳食补充剂或发酵食品(例如,黄色奶酪,发酵大豆-纳豆),并且是内生的,即,通过产生不断定植于人类大肠微生物组的细菌。本文主要研究由人类肠道微生物组中最活跃的成员合成的内源性K2。这项分析测试了86个肠道来源的细菌菌株,其中最大的VK2生产商(乳酸菌,双歧杆菌,选择芽孢杆菌)。此外,基于选择的VK2-MK4同源物,在没有脂肪共存的水性环境中,VK2渗透到Caco-2细胞中的潜力,胰酶,或胆汁盐已显示。测试了三种VK2同源物:VK2-MK4,VK2-MK7和VK2-MK9对Caco-2细胞凋亡和坏死的影响,证明了它们对测试细胞的有害作用。此外,长链同系物(VK2-MK9和VK2-MK7)在抑制促炎细胞因子如IL-8(对于Caco-2组织)和IL-6和TNFα(对于RAW264.7)分泌中的独特作用已被证明.
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