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    Home > Active Ingredient News > Antitumor Therapy > Sub-Journal of "Cell": This bacteria can really fight cancer!

    Sub-Journal of "Cell": This bacteria can really fight cancer!

    • Last Update: 2022-01-09
    • Source: Internet
    • Author: User
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    2022 is coming soon! (Roar-on the last day of 2021, are you sticking to work or sneaking fish? Anyway, singularity cake is thinking seriously-what good should I eat these days~ But, singularity The Chongqing hot pot on the cake side had just been arranged, and my friend had acute enteritis after eating fried rice noodles
    .

    In order to make him (bi) can (xu) arrive as scheduled in the hot pot bureau the day after tomorrow, Qidian cake hurriedly gave him When buying medicine, the pharmacy said that you can have some probiotics to eat, repair the intestinal mucosa, regulate the homeostasis of intestinal bacteria
    .

    Probiotics.
    .
    .
    this is a reminder of the singularity cake
    .

    Recently, an article published on Cancer Cell proposed , A kind of probiotics and their metabolites that naturally exist in our intestines-Lactobacillus reuteri and Reuterin, can also effectively inhibit the development of colorectal cancer (CRC) [1 ]
    .

    Yatrik M.
    Shah from the University of Michigan in the United States and his colleagues found that Lactobacillus reuteri and reuterin can induce oxidative stress in CRC cells and inhibit their ribose by consuming glutathione.
    It inhibits the progress of CRC
    .

    More importantly, oral administration of Lactobacillus reuteri to CRC mice can shrink the tumors of the mice and prolong the survival time
    .

    CRC is one of the most common malignant tumors.
    there are nearly two million new cases each year, the main reason is the world's cancer-related deaths [2]
    .

    Numerous studies show that, in patients with CRC with the progress of the disease, intestinal flora imbalance will occur; conversely, intestinal bacteria also in the development of CRC Plays an important role
    .

    For example, some pathogenic bacteria can disrupt the balance between pro-inflammatory and anti-inflammatory cytokines, cause damage to the mucosal barrier, etc.
    , further promote the progress of CRC, and limit the efficacy of immunotherapy [3]
    .

    If we can accurately understand what role intestinal bacteria play in the development of CRC, it may help to decipher the current status of CRC treatment
    .

    So how did Shah and his colleagues find Lactobacillus reuteri and reuterin? First, they used healthy mice, CRC mice (obtained by conditional gene knockout), and fecal metabolites from healthy people and CRC patients to process a variety of human cell lines in vitro
    .

    The results showed that the feces of healthy mice and healthy people can significantly inhibit the proliferation of the four CRC cells, HCT116, SW480, DLD1, and RKO, and induce apoptosis, while the feces of CRC mice and CRC patients have no obvious effect on these cells.
    Influence
    .

    Moreover, this inhibitory effect on cell proliferation only targets CRC cells, but does not inhibit the proliferation of healthy colorectal epithelial cells (NCM460 cell line)
    .

    Through metabolomics and other analysis of the feces of mice, the researchers determined that in the feces, reuterin is the main metabolite that inhibits the growth of CRC cells
    .

    C, D: The feces of healthy mice can effectively induce CRC cell death.
    E: CRC patients vs.
    the fecal metabolites of healthy people.
    Further research results show that whether it is CRC mice or CRC patients at different stages, it is compared with normal mice.
    Compared with human colorectal tissues, the levels of Lactobacillus reuteri and reuteriin in tumor tissues have decreased to varying degrees
    .

    In addition, comparing the tumor tissues of CRC patients with adjacent healthy tissues, it can also be found that the levels of Lactobacillus reuteri and reuterin in the tumor tissues are lower
    .

    It is worth mentioning that when the fecal metabolites of CRC mice are used to treat Lactobacillus reuteri in vitro, it can inhibit the growth and metabolism of Lactobacillus reuteri
    .

    In other words, Lactobacillus reuteri and reutericin have the effect of inhibiting the proliferation of CRC cells
    .

    However, in the CRC tumor environment, the growth of Lactobacillus reuteri was inhibited, and the activity of reuteri was also restricted.
    This explains why the feces of CRC mice cannot effectively inhibit the proliferation of CRC cells
    .

    E: Neighboring healthy tissue vs.
    tumor tissue.
    F: Healthy colorectal tissue vs.
    tumor tissue.
    Now that the target has been targeted, let’s take a closer look at how Lactobacillus reuteri and reuteri can fight cancer
    .

    Shah and his colleagues first used lactate dehydrogenase (LDH) testing to confirm that reuterin can indeed induce CRC cell death, and it can exert effective toxicity at a concentration of 25μM
    .

    You should know that in healthy colorectal tissues, the concentration of reuterin can reach 100μM
    .

    Not only that, but they reconfirmed in more types of human cell lines that healthy colorectal epithelial cells are significantly less sensitive to reuterin than CRC cells
    .

    And it was found that reuteri can also inhibit the growth of pancreatic ductal adenocarcinoma, lymphoma, ovarian cancer and melanoma cells to varying degrees; while breast cancer and cervical cancer cells have certain resistance to reuteri
    .

    B: Reustoin has an inhibitory effect on a variety of tumor cell lines.
    F: Reustoin will recognize "friendly" cells.
    From a mechanism point of view, reutetoin is a highly selective electrophilic The reagent can interact with cysteine ​​and consume glutathione, which will disrupt the redox balance in the cell
    .

    Researchers have observed in the human CRC cell line that when treated with Reuterin, the reactive oxygen species (ROS) components in CRC cells are significantly upregulated in a dose-dependent manner
    .

    However, when Reuteri was used to treat HeLa cells and normal colorectal epithelial cells, the intracellular ROS content did not increase
    .

    Further studies have found that the oxidative stress of CRC cells caused by reuterin can inhibit the proliferation of CRC cells by inducing protein oxidation, selectively inhibiting ribosomal activity and protein translation
    .

    Left: As CRC progresses, the levels of Lactobacillus reuteri and reuteri in the tumor tissue decrease.
    Right: Lactobacillus reuteri and the mechanism by which reuteri inhibits the development of CRC.
    Finally, Shah and his colleagues We gave Lactobacillus reuteri orally to CRC mice to observe the anti-cancer effects of Lactobacillus reuteri and reuteriin in vivo
    .

    They constructed a xenograft CRC mouse model by subcutaneously implanting a human CRC cell line
    .

    Subsequently, these mice were randomly divided into groups and fed with wild-type Lactobacillus reuteri and mutant Lactobacillus reuteri (the mutant type could not produce reuteri)
    .

    After 2 days of treatment, compared with the CRC mice fed with mutant Lactobacillus reuteri, the tumor growth of CRC mice fed with wild-type Lactobacillus reuteri began to be significantly inhibited; within the tumor, not only Reuteri The level of cytokine has been increased, and the content of pro-apoptotic factors cCaspase3 and ROS have also been greatly increased, while the homeostasis of neighboring healthy tissues has not been affected
    .

    Not only that, they also observed the same effect in other CRC mouse models (MC38, conditional gene knockout)
    .

    In the CRC mouse model constructed by conditional gene knockout, the survival period of mice treated with wild-type Lactobacillus reuteri was significantly prolonged, and their CRC intracellular protein translation levels were monitored to decrease, which is also consistent with in vitro experiments.
    The mechanism of exploration is consistent
    .

    A: The size of the tumor
    .

    B: The level of Roy's protein in the tumor
    .

    K: Survival rate of mice
    .

    L: ROS content in tumor
    .

    P: Protein translation.
    In general, Shah and his colleagues found that a probiotic and its metabolites in our intestines, Lactobacillus reuteri and Reuteri, can consume glutathione, Induces oxidative stress in colorectal cancer cells, resulting in protein oxidation and damage to ribosomal activity, thereby inhibiting the development of colorectal cancer
    .

    When mice with colorectal cancer were orally administered Lactobacillus reuteri, which can normally produce reuteri, the mice's condition was relieved, the tumors shrank and the survival time was prolonged
    .

    Regarding how Lactobacillus reuteri and reuteri "avoid" normal cells and only work on colorectal cancer cells, the researchers did not discuss in depth in this study
    .

    But they believe that this is related to changes in the metabolic environment of tumor cells
    .

    Singularity Cake believes that even by 2022, intestinal bacteria will still be active in various research fields
    .

    However, if oral probiotics can have anti-cancer effects-why not hurry up and study it? ! References: [1] Bell HN, et al.
    Reuterin in the healthy gut microbiome suppresses colorectal cancer growth through altering redox balance.
    Cancer Cell.
    2021 Dec 14:S1535-6108(21)00613-9.
    doi: 10.
    1016/j.
    ccell.
    2021.
    12.
    001.
    Epub ahead of print.
    PMID: 34951957.
    [2]Bray F, et al.
    Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
    CA Cancer J Clin.
    2018; 68:394–424.
    [3]Rebersek, M.
    Gut microbiome and its role in colorectal cancer.
    BMC Cancer 21, 1325 (2021).
    https://doi.
    org/10.
    1186/s12885-021-09054-2 Author of this article | Zhang Aidi
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