Short-chain fatty acids reprogram metabolic profiles with the induction of reactive oxygen species production in human colorectal adenocarcinoma cells

Huang, Chongyang; Deng, Wenjun; Xu, Huanzhou; Zhou, Chen; Zhang, Fan; Chen, Junfei; Bao, Qingjia; Zhou, Xin; Liu, Maili; Li, Jing; Liu, Chaoyang

doi:10.1016/j.csbj.2023.02.022

Cited by 16 publications

(8 citation statements)

References 110 publications

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“…MgA and NaP reduced ROS production in the AGS cells at all tested concentrations (3,000 μg/mL, 1,500 μg/mL, and 750 μg/mL; Figure 1 ). This is in contrast with previous studies which showed that MgA and NaP induced ROS production in Caco-2 colorectal cancer cells and mouse glomerular mesangialn cells ( 43 , 44 ). At all tested concentrations (3,000 μg/mL, 1,500 μg/mL, and 750 μg/mL), NaB significantly enhanced ROS production compared to the negative control ( p < 0.0001) suggesting that NaB may have pro-oxidative properties in the AGS cells ( Figure 1 ).…”

Section: Resultscontrasting

confidence: 99%

“…Oxidative stress is a hallmark of carcinogenesis. Reactive oxygen species (ROS) function as a significant biomarker in cancer and play a crucial role not only in the initiation of cancer but also in its progression and metastasis ( 43 ). Consequently, inhibiting the production of ROS by cancer cells is often regarded as a valuable approach for the development of novel anticancer drugs.…”

Section: Resultsmentioning

confidence: 99%

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The postbiotic sodium butyrate synergizes the antiproliferative effects of dexamethasone against the AGS gastric adenocarcinoma cells

Eladwy,

Alsherbiny,

Chang

et al. 2024

Front. Nutr.

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A growing body of literature underlines the fundamental role of gut microbiota in the occurrence, treatment, and prognosis of cancer. In particular, the activity of gut microbial metabolites (also known as postbiotics) against different cancer types has been recently reported in several studies. However, their in-depth molecular mechanisms of action and potential interactions with standard chemotherapeutic drugs remain to be fully understood. This research investigates the antiproliferative activities of postbiotics- short-chain fatty acid (SCFA) salts, specifically magnesium acetate (MgA), sodium propionate (NaP), and sodium butyrate (NaB), against the AGS gastric adenocarcinoma cells. Furthermore, the potential synergistic interactions between the most active SCFA salt-NaB and the standard drug dexamethasone (Dex) were explored using the combination index model. The molecular mechanisms of the synergy were investigated using reactive oxygen species (ROS), flow cytometry and biochemometric and liquid chromatography-mass spectrometry (LC–MS)-driven proteomics analyses. NaB exhibited the most significant inhibitory effect (p < 0.05) among the tested SCFA salts against the AGS gastric cancer cells. Additionally, Dex and NaB exhibited strong synergy at a 2:8 ratio (40 μg/mL Dex + 2,400 μg/mL NaB) with significantly greater inhibitory activity (p < 0.05) compared to the mono treatments against the AGS gastric cancer cells. MgA and NaP reduced ROS production, while NaB exhibited pro-oxidative properties. Dex displayed antioxidative effects, and the combination of Dex and NaB (2,8) demonstrated a unique pattern, potentially counteracting the pro-oxidative effects of NaB, highlighting an interaction. Dex and NaB individually and in combination (Dex:NaB 40:2400 μg/mL) induced significant changes in cell populations, suggesting a shift toward apoptosis (p < 0.0001). Analysis of dysregulated proteins in the AGS cells treated with the synergistic combination revealed notable downregulation of the oncogene TNS4, suggesting a potential mechanism for the observed antiproliferative effects. These findings propose the potential implementation of NaB as an adjuvant therapy with Dex. Further investigations into additional combination therapies, in-depth studies of the molecular mechanisms, and in vivo research will provide deeper insights into the use of these postbiotics in cancer, particularly in gastric malignancies.

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Section: Resultscontrasting

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The postbiotic sodium butyrate synergizes the antiproliferative effects of dexamethasone against the AGS gastric adenocarcinoma cells

Eladwy,

Alsherbiny,

Chang

et al. 2024

Front. Nutr.

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“…ROS is a term to describe a series of oxygen-containing compounds with high oxidative properties produced during cell metabolism, mainly including hydroxyl radicals, superoxide anions, and hydrogen peroxide, which play a vital role in regulating many signaling pathways in maintaining the homeostasis of the intestine [ 55 ]. Some previous studies on the mechanism of SCFAs have focused on specific metabolites or genes involved in improving the therapeutic effect of colitis, such as reactive oxygen species (ROS) biosynthesis [ 56 ]. A previous study showed that SCFA induces apoptosis and activates autophagy in colitis [ 57 ].…”

Section: Scfa-mediated Immune Regulation Plays a Key Role In Maintain...mentioning

confidence: 99%

Short Chain Fatty Acids: Essential Weapons of Traditional Medicine in Treating Inflammatory Bowel Disease

Yao,

Liu,

et al. 2024

Molecules

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Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal inflammatory disease, mainly including Crohn’s disease (CD) and ulcerative colitis (UC). In recent years, the incidence and prevalence of IBD have been on the rise worldwide and have become a significant concern of health and a huge economic burden on patients. The occurrence and development of IBD involve a variety of pathogenic factors. The changes in short-chain fatty acids (SCFAs) are considered to be an important pathogenic mechanism of this disease. SCFAs are important metabolites in the intestinal microbial environment, which are closely involved in regulating immune, anti-tumor, and anti-inflammatory activities. Changes in metabolite levels can reflect the homeostasis of the intestinal microflora. Recent studies have shown that SCFAs provide energy for host cells and intestinal microflora, shape the intestinal environment, and regulate the immune system, thereby regulating intestinal physiology. SCFAs can effectively reduce the incidence of enteritis, cardiovascular disease, colon cancer, obesity, and diabetes, and also play an important role in maintaining the balance of energy metabolism (mainly glucose metabolism) and improving insulin tolerance. In recent years, many studies have shown that numerous decoctions and natural compounds of traditional Chinese medicine have shown promising therapeutic activities in multiple animal models of colitis and thus attracted increasing attention from scientists in the study of IBD treatment. Some of these traditional Chinese medicines or compounds can effectively alleviate colonic inflammation and clinical symptoms by regulating the generation of SCFAs. This study reviews the effects of various traditional Chinese medicines or bioactive substances on the production of SCFAs and their potential impacts on the severity of colonic inflammation. On this basis, we discussed the mechanism of SCFAs in regulating IBD-associated inflammation, as well as the related regulatory factors and signaling pathways. In addition, we provide our understanding of the limitations of current research and the prospects for future studies on the development of new IBD therapies by targeting SCFAs. This review may widen our understanding of the effect of traditional medicine from the view of SCFAs and their role in alleviating IBD animal models, thus contributing to the studies of IBD researchers.

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“…Detrimental opportunistic pathogens can reconstruct the composition of colonic commensal bacteria, thus favoring the creation of a microenvironment susceptible to carcinogenesis. Conventional CRC treatments are Acetate was shown to reduce CRC proliferation and induce apoptosis, as indicated by several features such as loss of mitochondrial membrane potential, nuclear chromatin condensation, and ROS generation [253]. Upon acetate treatment, CRC cells exhibit apoptosis-related morphological features, while lysosomal membrane permeabilization with subsequent cathepsin D release in the cytosol takes place [254].…”

Section: Challenges and Future Perspectivesmentioning

confidence: 99%

Probiotic-Derived Bioactive Compounds in Colorectal Cancer Treatment

Thoda

Touraki

2023

Microorganisms

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Colorectal cancer (CRC) is a multifactorial disease with increased morbidity and mortality rates globally. Despite advanced chemotherapeutic approaches for the treatment of CRC, low survival rates due to the regular occurrence of drug resistance and deleterious side effects render the need for alternative anticancer agents imperative. Accumulating evidence supports that gut microbiota imbalance precedes the establishment of carcinogenesis, subsequently contributing to cancer progression and response to anticancer therapy. Manipulation of the gut microbiota composition via the administration of probiotic-derived bioactive compounds has gradually attained the interest of scientific communities as a novel therapeutic strategy for CRC. These compounds encompass miscellaneous metabolic secreted products of probiotics, including bacteriocins, short-chain fatty acids (SCFAs), lactate, exopolysaccharides (EPSs), biosurfactants, and bacterial peptides, with profound anti-inflammatory and antiproliferative properties. This review provides a classification of postbiotic types and a comprehensive summary of the current state of research on their biological role against CRC. It also describes how their intricate interaction with the gut microbiota regulates the proper function of the intestinal barrier, thus eliminating gut dysbiosis and CRC development. Finally, it discusses the future perspectives in precision-medicine approaches as well as the challenges of their synthesis and optimization of administration in clinical studies.

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Short-chain fatty acids reprogram metabolic profiles with the induction of reactive oxygen species production in human colorectal adenocarcinoma cells

Cited by 16 publications

References 110 publications

The postbiotic sodium butyrate synergizes the antiproliferative effects of dexamethasone against the AGS gastric adenocarcinoma cells

The postbiotic sodium butyrate synergizes the antiproliferative effects of dexamethasone against the AGS gastric adenocarcinoma cells

Short Chain Fatty Acids: Essential Weapons of Traditional Medicine in Treating Inflammatory Bowel Disease

Probiotic-Derived Bioactive Compounds in Colorectal Cancer Treatment

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