Short-chain fatty acids and cancer

Trends in cancer, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

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Gut dysbiosis conveys psychological stress to activate LRP5/β-catenin pathway promoting cancer stemness

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 5, 2025

Psychological stress causes gut microbial dysbiosis and cancer progression, yet how microbiota determines psychological stress-induced tumor development remains unclear. Here we showed that promotes breast growth stemness, an outcome depends on in germ-free antibiotic-treated mice. Metagenomic metabolomic analyses revealed markedly alters the composition abundance of microbiota, especially Akkermansia muciniphila (A. muciniphila), decreases short-chain fatty acid butyrate. Supplement active A. muciniphila, butyrate or a butyrate-producing high fiber diet dramatically reversed oncogenic property anxiety-like behavior murine spontaneous model orthotopic model. Mechanistically, RNA sequencing analysis screened out LRP5 expression to block activation Wnt/β-catenin signaling pathway, dampening stemness. Moreover, as HDAC inhibitor elevated histone H3K9 acetylation level transcriptionally activate ZFP36, which further accelerates mRNA decay by binding adenine uridine-rich (AU-rich) elements transcript. Clinically, fecal serum were inversely correlated with tumoral LRP5/β-catenin expression, poor prognosis negative mood patients. Altogether, our findings uncover microbiota-dependent mechanism stress-triggered provide both clinical biomarkers potential therapeutic avenues for patients undergoing stress.

Language: Английский

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Sodium butyrate and sodium propionate inhibit breast cancer cell migration and invasion through regulation of epithelial-to-mesenchymal transition and suppression of MEK/ERK signaling pathway

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: March 12, 2025

Objective This study aims to investigate the roles played by NaB and NaP in breast carcinogenesis elucidating their potential anti-metastatic effects context of tumor migration, invasion, EMT regulation two distinct cancer cell lines, MCF-7 MDA-MB-231. Methods The cytotoxic effect both compounds on 3D spheroid formation was evaluated using a hanging drop assay. anti-migratory anti-invasive potentials were investigated through transwell migration invasion assays. Moreover, role regulating epithelial-to-mesenchymal transition (EMT) examined assessing E-cadherin, vimentin, β-catenin mRNA protein expression levels RT-qPCR Western blot or flow cytometry. β-Catenin localization upon treatment further visualized via immunofluorescence. Protein MEK, p-MEK, ERK, p-ERK analyzed blot. Results Our results revealed dose- time-dependent impairment with exerting more potent than NaP. Both SCFAs able significantly inhibit MDA-MB-231 cells following 24 h treatment. altered profile EMT-associated markers abrogated nuclear translocation β-catenin. Finally, ERK MEK phosphorylation reduced NaB, less prominently Conclusion highlights promising therapeutic NaP, providing insight into inhibitory formation, deactivation MEK/ERK signaling cancer.

Language: Английский

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The butyrate derived from probiotic Clostridium butyricum exhibits an inhibitory effect on multiple myeloma through cell death induction

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 7, 2025

Multiple myeloma (MM) is a hematological malignancy characterized by poor prognosis. While certain probiotics have been shown to produce antitumor molecules that inhibit solid tumor progression, it remains unclear whether probiotic-derived compounds can exert similar effects on tumors, such as MM. In this study, we screened the cell-free culture supernatants (CFCS) of 24 probiotic strains for against multiple cells and identified CFCS from Clostridium butyricum (C. butyricum) demonstrated most significant reduction in MM cell viability. Further fractionation through reverse-phase gel filtration chromatography revealed high enrichment butyrate fraction, confirmed gas chromatography-mass spectrometry. Butyrate reduced viability concentration-dependent manner. was significantly more cytotoxic RPMI-8226 than peripheral blood mononuclear (PBMCs) isolated two non-cancerous individuals. xenograft model cells, showed inhibition formation. Cell cycle analysis induced G1 phase arrest increased sub-G1 phase, suggesting DNA fragmentation. Western blot treatment led cleaved poly ADP-ribose polymerase (PARP) accumulation. Additionally, flow cytometry an increase annexin V positive indicating apoptosis. also exhibited synergistic activity when combined with bortezomib, proteasome inhibitor. These findings suggest molecules, including butyrate, may enhance therapeutic effect malignancy,

Language: Английский

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Emerging Role of Gut Microbiota in Breast Cancer Development and Its Implications in Treatment

Metabolites, Journal Year: 2024, Volume and Issue: 14(12), P. 683 - 683

Published: Dec. 5, 2024

Background: The human digestive system contains approximately 100 trillion bacteria. gut microbiota is an emerging field of research that associated with specific biological processes in many diseases, including cardiovascular disease, obesity, diabetes, brain rheumatoid arthritis, and cancer. Emerging evidence indicates the affects response to anticancer therapies by modulating host immune system. Recent studies have explained a high correlation between breast cancer: dysbiosis cancer may regulate systemic inflammatory response, hormone metabolism, tumor microenvironment. Some bacteria are related estrogen which increase or decrease risk changing number hormones. Further, has been seen modulate respect its ability protect against treat cancers, focus on receptor-positive Probiotics other claiming control microbiome bacterial means might be useful prevention, even treatment, Conclusions: present review underlines various aspects clinical application, warranting individualized microbiome-modulated therapeutic approaches treatment.

Language: Английский

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The Link Between the Gut Microbiome and Bone Metastasis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12086 - 12086

Published: Nov. 11, 2024

The gut microbiome is essential for regulating host metabolism, defending against pathogens, and shaping the host's immune system. Mounting evidence highlights that disruption in microbial communities significantly impacts cancer development treatment. Moreover, tumor-associated microbiota, along with its metabolites toxins, may contribute to progression by promoting epithelial-to-mesenchymal transition, angiogenesis, metastatic spread distant organs. Bones, particular, are common sites metastasis due a rich supply of growth neovascularization factors extensive blood flow, especially affecting patients thyroid, prostate, breast, lung, kidney cancers, where bone metastases severely reduce quality life. While involvement formation still being explored, proposed mechanisms suggest intestinal dysbiosis alter microenvironment via gut-immune-bone axis, fostering premetastatic niche immunosuppressive milieu suitable cell colonization. Disruption delicate balance modeling remodeling further create favorable environment growth. This review focuses on link between beneficial or dysbiotic composition homeostasis, as well role development. It also provides an overview clinical trials evaluating impact community structure parameters across various conditions health-related issues. Dietary interventions microbiota modulation probiotics, prebiotics, fecal transplantation help support health might offer promising strategies addressing bone-related complications cancer.

Language: Английский

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Elucidating the evolving role of cuproptosis in breast cancer progression

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(12), P. 4872 - 4887

Published: Jan. 1, 2024

Breast cancer (BC) persists as a highly prevalent malignancy in females, characterized by diverse molecular signatures and necessitating personalized therapeutic approaches. The equilibrium of copper within the organism is meticulously maintained through regulated absorption, distribution, elimination, underpinning not only cellular but also various essential biological functions. process cuproptosis initiated copper's interaction with lipoylases tricarboxylic acid (TCA) cycle, which triggers conglomeration lipoylated proteins diminishes integrity Fe-S clusters, culminating cell demise proteotoxic stress. In BC, aberrations are prominent represent crucial incident that contributes to disease progression. It influences BC metabolism affects critical traits such proliferation, invasiveness, resistance chemotherapy. Therapeutic strategies target have shown promising antitumor efficacy. Moreover, plethora cuproptosis-centric genes, including cuproptosis-related genes (CRGs), CRG-associated non-coding RNAs (ncRNAs), cuproptosis-associated regulators, been identified, offering potential for development risk assessment models or diagnostic signatures. this review, we provide comprehensive exposition fundamental principles cuproptosis, its influence on malignant phenotypes prognostic implications cuproptosis-based markers, substantial prospects exploiting therapy, thereby laying theoretical foundation targeted interventions domain.

Language: Английский

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Targeting cuproptosis for cancer therapy: Focus on the anti-tumor immune system

Cancer Pathogenesis and Therapy, Journal Year: 2024, Volume and Issue: unknown

Published: July 1, 2024

Copper (Cu) is an indispensable micronutrient that maintains signaling pathways and biological homeostasis in almost all cell types; however, its excess affects the tricarboxylic acid cycle, causes accumulation of fatty acylated proteins, destabilization iron–sulfur cluster increases levels intracellular reactive oxygen species, leading to proteotoxic stress death. Cuproptosis, a form Cu-dependent death, differs from other types regulated death (RCD) was first reported Science 2022. Recently, RCD have been targeted cancer therapy. However, escape apoptosis tumor cells resistance treatment recurrence. Therefore, there urgent need study alternative mechanisms mortality. Compared normal patients, significant increase serum Cu ion has observed patients with tumors. Moreover, proliferation, angiogenesis, metastasis are associated cuproptosis. Thus, exploring related cuproptosis will provide new perspective for development anti-cancer drugs. Importantly, closely modulation anti-tumor immunity. The expression cuproptosis-related genes (CRGs) significantly correlated immune infiltration checkpoint programmed protein 1 (PD-1)/programmed death-ligand (PD-L1). Based on these findings, series drugs used tumor-targeted combination therapy or as synergists. elucidating role per stage microenvironment (TIME) helpful clarifying potential value specific cancers. In this review, we summarize based regulation concentration. two approaches may help researchers develop more therapies targeting pathways. focused effect TIME systematically discussed CRGs immunity considering CRG-related pathways, prognosis scoring system, immunotherapy, experiments bioinformatics prediction models, ideas anticancer

Language: Английский

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