Potential Mechanisms of Probiotics Action in the Prevention and Treatment of Colorectal Cancer

Colorectal cancer is one of the most common and most diagnosed cancers in the world. There are many predisposing factors, for example, genetic predisposition, smoking, or a diet rich in red, processed meat and poor in vegetables and fruits. Probiotics may be helpful in the prevention of cancer and may provide support during treatment. The main aim of this study is to characterize the potential mechanisms of action of probiotics, in particular the prevention and treatment of colorectal cancer. Probiotics’ potential mechanisms of action are, for example, modification of intestinal microbiota, improvement of colonic physicochemical conditions, production of anticancerogenic and antioxidant metabolites against carcinogenesis, a decrease in intestinal inflammation, and the production of harmful enzymes. The prevention of colorectal cancer is associated with favorable quantitative and qualitative changes in the intestinal microbiota, as well as changes in metabolic activity and in the physicochemical conditions of the intestine. In addition, it is worth noting that the effect depends on the bacterial strain, as well as on the dose administered.

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Phytotherapy for colorectal cancer: about some phytochemicals and their mechanisms of action]

Medicinal Plant Communications ◽

10.37360/mpc.20.3.3.15 ◽

2020 ◽

Vol 3 (4) ◽

pp. 79-84

Author(s):

Patricia Landazuri ◽

◽

Beatriz Restrepo ◽

Nelsy Loango ◽

◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Signaling Pathways ◽

Intestinal Microbiota ◽

Functional Foods ◽

Molecular Targets ◽

Mechanisms Of Action ◽

Inflammatory Signaling ◽

Men And Women ◽

Prevention And Treatment

Colorectal cancer (CRC) is very common in both men and women. Phytochemicals such as polysaccharide alkaloids, polyphenols, diterpenoids among others, have been used for the prevention and treatment of cancer. The mechanisms of action of these compounds on cancer cells include molecular targets in the apoptosis, proliferation, metastasis and anti-inflammatory signaling pathways. At the level of the whole organism, they improve the intestinal microbiota, which plays an important role in the initiation and progression of CRC. Recent research is aimed at obtaining and modifying phytochemicals to improve their effectiveness, safety and their inclusion in functional foods, but more studies are needed to validate their properties.

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Role of Natural Stilbenes in the Prevention of Cancer

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/3128951 ◽

2016 ◽

Vol 2016 ◽

pp. 1-15 ◽

Cited By ~ 64

Author(s):

J. Antoni Sirerol ◽

María L. Rodríguez ◽

Salvador Mena ◽

Miguel A. Asensi ◽

José M. Estrela ◽

...

Keyword(s):

Mechanisms Of Action ◽

Pharmacological Activities ◽

Important Group ◽

Prevention And Treatment ◽

Low Toxicity ◽

Prevention Of Cancer ◽

Novel Drug ◽

Improve Stability

Natural stilbenes are an important group of nonflavonoid phytochemicals of polyphenolic structure characterized by the presence of a 1,2-diphenylethylene nucleus. Stilbenes have an extraordinary potential for the prevention and treatment of different diseases, including cancer, due to their antioxidant, cell death activation, and anti-inflammatory properties which associate with low toxicity underin vivoconditions. This review aims to discuss various approaches related to their mechanisms of action, pharmacological activities in animal models and humans, and potential chemoprevention in clinical studies. The biological activity of natural stilbenes is still incompletely understood. Furthermore, after administration to animals or humans, these molecules are rapidly metabolized. Thus pharmacokinetics and/or activities of the natural structures and their metabolites may be very different. Novel drug formulations have been postulated in order to improve stability and bioavailability, to minimize side effects, and to facilitate interaction with their domains in target proteins. These pharmacological improvements should lead stilbenes to become effective candidates as anticancer drugs.

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The Association between Gut Microbiota and Intestinal Toll-like Receptors Genes Expression in Adenomatous and Colorectal Cancerous patients

10.21203/rs.2.23741/v1 ◽

2020 ◽

Author(s):

Sama Rezasoltani ◽

Maryam Sharafkhah ◽

Hamid Asadzadeh Aghdaei ◽

Meysam Olfatifar ◽

Ehsan Nazemalhosseini Mojarad ◽

...

Keyword(s):

Colorectal Cancer ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Intestinal Inflammation ◽

Inflammatory Responses ◽

Bacteroides Fragilis ◽

Normal Group ◽

Adenomatous Polyposis ◽

Toll Like Receptors ◽

Genes Expression

Abstract Background: Toll-like receptor (TLR) signaling has been implicated in colorectal cancer (CRC) development. Intestinal microbiota can affect the expression of TLRs, which may induce inflammatory responses and impair the gut homeostasis. Here, we aimed to evaluate certain intestinal microbiota related to TLRs expression in colonic tissues of adenomatous polyposis and CRC patients. Results: Fecal and colonic tissue samples were collected from normal controls (NC), adenomatous (AP) cases and (CRC) patients via colonoscopy for CRC screening during 2016 to 2018. Fecal samples were collected to analyze intestinal bacteria including Streptococcus bovis , Enterococcus faecalis , Bacteroides fragilis , enterotoxigenic Bacteroides fragilis (ETBF) , Fusobacterium nucleatum , Porphyromonas gingivalis, Porphyromonas spp . and Roseburia spp . by real-time PCR. Gene expression of TLR2, TLR4 and TLR5 was examined in colonic tissues by qRT-PCR. Different abundant of gut bacteria were achieved in NC, AP and CRC groups. The genes expression of TLR2, TLR4 and TLR5 were significantly different in AP and CRC cases vs. normal group (P value <0.05). There was a significant relationship between TLR2, TLR4, TLR5 genes expression and Roseburia spp., P. gingivalis and ETBF quantity in normal group. Also significant association between TLR2, TLR4 genes expression levels and the quantity of S.bovis , ETBF, Roseburia spp. and E. faecalis in AP and CRC cases were achieved. Conclusion : Intestinal expression of TLR2, TLR4 and TLR5 is dynamic and depends on gut microbiota. Hence, altered immune activation in response to dysbiotic microbiota may promote intestinal inflammation in a group of patients with AP and CRC. Keyword: Adenomatous polyposis; colorectal cancer; gut microbiota; Toll-like receptors; intestinal inflammation

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Ascorbic acid in the prevention and treatment of cancer

Revista da Associação Médica Brasileira ◽

10.1590/1806-9282.62.07.680 ◽

2016 ◽

Vol 62 (7) ◽

pp. 680-686 ◽

Cited By ~ 12

Author(s):

Ana Maria Oliveira Ferreira da Mata ◽

Ricardo Melo de Carvalho ◽

Marcus Vinícius Oliveira Barros de Alencar ◽

Ana Amélia de Carvalho Melo Cavalcante ◽

Benedito Borges da Silva

Keyword(s):

Ascorbic Acid ◽

Dose Response ◽

Clinical Studies ◽

Antitumor Agent ◽

Mechanisms Of Action ◽

Systematic Mapping ◽

Treatment And Prevention ◽

Prevention And Treatment ◽

Prevention Of Cancer

Summary This review is aimed at the systematic mapping of ascorbic acid in the prevention and/or treatment of cancer in clinical and non-clinical studies from 2011 to 2015, in order to understand dose-response variations as well as its mechanisms of action as an antioxidant and antitumor agent. Seventy-eight articles were retrieved from the PubMed/Bireme database, of which only 30 included ascorbic acid in the prevention and/or treatment of cancer. However, there are controversies regarding doses and a lack of clinical studies featuring its mechanism of action more clearly. Other studies are needed to understand dose-response variations, as well as its targeting mechanisms of action, both as an antioxidant and antitumor agent, to assist treatment and prevention of cancer, aiming at better quality of life for both patients and the general population.

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Foes or Friends? Bacteria Enriched in the Tumor Microenvironment of Colorectal Cancer

Cancers ◽

10.3390/cancers12020372 ◽

2020 ◽

Vol 12 (2) ◽

pp. 372 ◽

Cited By ~ 4

Author(s):

Xu ◽

Yin ◽

Zhang ◽

Lv ◽

Yang ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Microenvironment ◽

Human Health ◽

16S Rdna ◽

Intestinal Microbiota ◽

Intestinal Bacteria ◽

16S Rdna Sequencing ◽

Sequencing Data ◽

Rdna Sequencing ◽

Prevention And Treatment

Colorectal cancer (CRC) is the second most commonly diagnosed cancer and the third cause of cancer death in the world, while intestinal microbiota is a community of microbes living in human intestine that can potentially impact human health in many ways. Accumulating evidence suggests that intestinal microbiota, especially that from the intestinal bacteria, play a key role in the CRC development; therefore, identification of bacteria involved in CRC development can provide new targets for the CRC diagnosis, prevention, and treatment. Over the past decade, there have been considerable advances in applying 16S rDNA sequencing data to verify associated intestinal bacteria in CRC patients; however, due to variations of individual and environment factors, these results seem to be inconsistent. In this review, we scrutinized the previous 16S rDNA sequencing data of intestinal bacteria from CRC patients, and identified twelve genera that are specifically enriched in the tumor microenvironment. We have focused on their relationship with the CRC development, and shown that some bacteria could promote CRC development, acting as foes, while others could inhibit CRC development, serving as friends, for human health. Finally, we highlighted their potential applications for the CRC diagnosis, prevention, and treatment.

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Laminin 521 Modulates the Сytotoxic Effect of 5-Fluorouracil on Colorectal Cancer HT29 Cells

Biotekhnologiya ◽

10.21519/0234-2758-2019-35-6-73-79 ◽

2019 ◽

Vol 35 (6) ◽

pp. 73-79

Author(s):

A. Turchinovich ◽

I.M. Tsypina ◽

V.G. Zgoda ◽

S.V. Nikulin ◽

D.V. Maltseva

Keyword(s):

Colorectal Cancer ◽

Cytotoxic Effect ◽

Mechanisms Of Action ◽

Ht29 Cell ◽

Β1 Integrin ◽

Russian Science ◽

Apoptotic Gene ◽

Ht29 Cells ◽

First Time ◽

Ht29 Cell Line

The cytotoxic effect of 5-fluorouracil (5FU) and regorafenib (RF)-drugs with different mechanisms of action used to treat colorectal cancer-on the HT29 cell line when cultured on plastic and laminin 521 (LM-521) has been studied. It was shown for the first time that LM-521 can increase the sensitivity of tumor cells to 5FU. Based on the analysis of the transcriptome and proteome, a possible mechanism of the observed effect of LM-521 on HT29 cell viability was proposed. The interaction of β1-containing integrins on the cell surface with LM-521 can activate the FAK/PI3K/Akt signaling pathways, promote phosphorylation of the YAP transcription coactivator and its binding to a complex with the 14-3-3σ protein. The formation of such complex leads to the YAP retention in the cytoplasm, prevents its transport to the nucleus and the activation of anti-apoptotic gene transcription. apoptosis, β1 integrin, colorectal cancer, laminin 521 (laminin-11), regorafenib, 5-fluorouracil, HT29, ITGB1, LAMA5, YAP, SFN, 14-3-3σ The study was funded by the Russian Science Foundation (Project 17-14-01338).

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Modulation of Gut Microbiota for the Prevention and Treatment of COVID-19

Journal of Clinical Medicine ◽

10.3390/jcm10132903 ◽

2021 ◽

Vol 10 (13) ◽

pp. 2903

Author(s):

Jiezhong Chen ◽

Luis Vitetta

Keyword(s):

Clinical Trials ◽

Trace Elements ◽

Gut Microbiota ◽

Human Health ◽

Intestinal Microbiota ◽

Narrative Review ◽

Bacterial Metabolites ◽

Gut Dysbiosis ◽

Prevention And Treatment

The gut microbiota is well known to exert multiple benefits on human health including protection from disease causing pathobiont microbes. It has been recognized that healthy intestinal microbiota is of great importance in the pathogenesis of COVID-19. Gut dysbiosis caused by various reasons is associated with severe COVID-19. Therefore, the modulation of gut microbiota and supplementation of commensal bacterial metabolites could reduce the severity of COVID-19. Many approaches have been studied to improve gut microbiota in COVID-19 including probiotics, bacterial metabolites, and prebiotics, as well as nutraceuticals and trace elements. So far, 19 clinical trials for testing the efficacy of probiotics and synbiotics in COVID-19 prevention and treatment are ongoing. In this narrative review, we summarize the effects of various approaches on the prevention and treatment of COVID-19 and discuss associated mechanisms.

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Patients’ Awareness Of The Prevention And Treatment Of Colorectal Cancer*

Polish Journal of Surgery ◽

10.1515/pjs-2015-0088 ◽

2015 ◽

Vol 87 (9) ◽

Cited By ~ 3

Author(s):

Łukasz Dziki ◽

Anna Puła ◽

Konrad Stawiski ◽

Barbara Mudza ◽

Marcin Włodarczyk ◽

...

Keyword(s):

Colorectal Cancer ◽

Risk Factors ◽

Treatment Process ◽

Significant Negative Correlation ◽

Study Group ◽

Case Record ◽

High Incidence ◽

Prevention And Treatment ◽

Major Factors ◽

Medical University

Abstractwas to assess patients’ awareness of the prevention and treatment of colorectal cancer.Patients diagnosed with colorectal cancer, hospitalised at the Department of General and Colorectal Surgery of the Medical University in Łódź during the period from January 2015 to April 2015, were asked to complete a questionnaire concerning their families’ medical case record, factors predisposing them to the development of colorectal cancer, the tests applied in diagnostics, and the treatment process. The questionnaire comprised 42 closed-ended questions with one correct answer. A statistical analysis of all answers was carried out.The study group consisted of 30 men and 20 women aged 27–94 years old. A strong, statistically significant negative correlation between a patient’s age and his/her awareness of the prevention and treatment of colorectal cancer was noted (p<0.001; r= −0.51). The study demonstrated a statistically significant relationship between the occurrence of neoplasms in a patient’s family (p=0.009) or, more specifically, the occurrence of colorectal cancer (p=0.008), and the awareness of the prevention programme. The women’s group was characterised by statistically significantly greater awareness of colonoscopy as a screening examination (p=0.004).Patients need more information on colorectal cancer, its risk factors, prevention, the treatment process, and postoperative care. Lack of awareness of the colorectal cancer issue can be one of the major factors contributing to the high incidence of this disease.

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Signaling pathways in intestinal homeostasis and colorectal cancer: KRAS at centre stage

Cell Communication and Signaling ◽

10.1186/s12964-021-00712-3 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Camille Ternet ◽

Christina Kiel

Keyword(s):

Colorectal Cancer ◽

Signaling Pathways ◽

Intestinal Microbiota ◽

Critical Role ◽

Neuroendocrine Cells ◽

Cell Junction ◽

Intestinal Cell ◽

Intestinal Homeostasis ◽

Cell Functions ◽

The Impact

AbstractThe intestinal epithelium acts as a physical barrier that separates the intestinal microbiota from the host and is critical for preserving intestinal homeostasis. The barrier is formed by tightly linked intestinal epithelial cells (IECs) (i.e. enterocytes, goblet cells, neuroendocrine cells, tuft cells, Paneth cells, and M cells), which constantly self-renew and shed. IECs also communicate with microbiota, coordinate innate and adaptive effector cell functions. In this review, we summarize the signaling pathways contributing to intestinal cell fates and homeostasis functions. We focus especially on intestinal stem cell proliferation, cell junction formation, remodelling, hypoxia, the impact of intestinal microbiota, the immune system, inflammation, and metabolism. Recognizing the critical role of KRAS mutants in colorectal cancer, we highlight the connections of KRAS signaling pathways in coordinating these functions. Furthermore, we review the impact of KRAS colorectal cancer mutants on pathway rewiring associated with disruption and dysfunction of the normal intestinal homeostasis. Given that KRAS is still considered undruggable and the development of treatments that directly target KRAS are unlikely, we discuss the suitability of targeting pathways downstream of KRAS as well as alterations of cell extrinsic/microenvironmental factors as possible targets for modulating signaling pathways in colorectal cancer.

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A Crosstalk between Diet, Microbiome and microRNA in Epigenetic Regulation of Colorectal Cancer

Nutrients ◽

10.3390/nu13072428 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2428

Author(s):

Małgorzata Guz ◽

Witold Jeleniewicz ◽

Anna Malm ◽

Izabela Korona-Glowniak

Keyword(s):

Colorectal Cancer ◽

Gastrointestinal Tract ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Current Knowledge ◽

Vital Role ◽

Disease States ◽

Health And Disease ◽

Dietary Components ◽

Non Coding Rnas

A still growing interest between human nutrition in relation to health and disease states can be observed. Dietary components shape the composition of microbiota colonizing our gastrointestinal tract which play a vital role in maintaining human health. There is a strong evidence that diet, gut microbiota and their metabolites significantly influence our epigenome, particularly through the modulation of microRNAs. These group of small non-coding RNAs maintain cellular homeostasis, however any changes leading to impaired expression of miRNAs contribute to the development of different pathologies, including neoplastic diseases. Imbalance of intestinal microbiota due to diet is primary associated with the development of colorectal cancer as well as other types of cancers. In the present work we summarize current knowledge with particular emphasis on diet-microbiota-miRNAs axis and its relation to the development of colorectal cancer.

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