Lactobacillus-derived metabolites enhance the antitumor activity of 5-FU and inhibit metastatic behavior in 5-FU-resistant colorectal cancer cells by regulating claudin-1 expression

An, JaeJin; Ha, Eun Mi

doi:10.1007/s12275-020-0375-y

Cited by 15 publications

(9 citation statements)

References 48 publications

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“…To validate the response of PDOs to anticancer agents in vitro , we executed quantitative comparisons of cellular viabilities in five PDOs treated with the standard chemotherapeutics 5-FU, − oxaliplatin, − and irinotecan , (Figure ). In this part, samples CRC-20, CRC-31, CRC-41, CRC-52, and CRC-53 were chosen because we obtained a better-growing status of the PDOX model using these five samples.…”

Section: Results and Discussionmentioning

confidence: 99%

Patient-Derived Organoid Model in the Prediction of Chemotherapeutic Drug Response in Colorectal Cancer

Hao

Cao²,

Wang

et al. 2022

ACS Biomater. Sci. Eng.

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As an emerging technology in precision medicine, the patient-derived organoid (PDO) technology has been indicated to provide novel modalities to judge the sensitivity of individual tumors to cancer drugs. In this work, an in vitro model of colorectal cancer (CRC) was established using the PDO culture, and it is demonstrated that the PDO samples preserved, to a great extent, the histologic features and marker expression of the original tumor tissues. Subsequently, cancer drugs 5-FU, oxaliplatin, and irinotecan were selected and screened on five CRC PDO samples, while the patient-derived organoid xenograft (PDOX) model was applied for comparison. The receiver operating characteristic (ROC) curve was drawn according to the IC 50 data from the PDO model and the relative tumor proliferation rate (T/C%) from PDOX. Interestingly, the area under the ROC curve was 0.84 (95% CI, 0.64−1.04, P value = 0.028), which suggested that the IC 50 of cancer drugs from the PDO model was strongly correlated with PDOX responses. In addition, the optimal sensitivity cutoff value for drug screening in CRC PDOs was identified at 10.35 μM, which could act as a reference value for efficacy evaluation of 5-FU, oxaliplatin, and irinotecan in the colorectal cancer drug screening. Since there are no unified criteria to judge the sensitivity of drugs in vitro, our work provides a method for establishing in vitro evaluation criteria via PDO and PDOX model using the patient tissues received from local hospitals, exhibiting potential in clinical cancer therapy and precision medicine.

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Section: Results and Discussionmentioning

confidence: 99%

Patient-Derived Organoid Model in the Prediction of Chemotherapeutic Drug Response in Colorectal Cancer

Hao

Cao²,

Wang

et al. 2022

ACS Biomater. Sci. Eng.

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“…CLDN1 is an oncogene in CRC, and it can regulate the occurrence and development of CRC by multiple biological effects on processes such as the EMT. 31 We obtained a more comprehensive biological mechanism by employing CLDN1 and its co-expressed genes to explore the molecular mechanism of enhancers in CRC radiation resistance. A total of 398 coexpressed genes of CLDN1 were calculated based on the data from radio-treated patients with CRC and intersected with the regulatory genes of the enhancer.…”

Section: Discussionmentioning

confidence: 99%

“…The process for screening public data was based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline, and the last screening of the public data was on January 10, 2021. Previous research has shown that CLDN1 is an oncogene in CRC, [31][32][33][34]37,38 but the latest expression profile of CLDN1 in CRC is still unavailable, given the rapid development of high-throughput data. Therefore, the high-throughput arrays and the highthroughput RNA-sequencing data of CRC were obtained from The Cancer Genome Atlas (TCGA), GEO, ArrayExpress, and Sequence Read Archive to assess the expression status of CLDN1 in CRC patients.…”

Section: The High-throughput Data Of Cldn1 Expression In Colorectal Cancermentioning

confidence: 99%

“…CLDN1 functions as a carcinogenic factor and could promote various malignant tumors, including CRC, by promoting the epithelialmesenchymal transition (EMT), by activation of transcription factors in the colonic epithelium, or by the anoikis pathways. [31][32][33] Ouban et al indicated that CLDN1 was an initiating factor for early CRC and that a high expression of CLDN1 could be detected in early-stage CRC. 34 CLDN1 expression is boosted by promoters and enhancers in CRC, 35 indicating that an enhancer might affect CRC by regulating genes like CLDN1.…”

Section: Introductionmentioning

confidence: 99%

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Active Enhancer Assessment by H3K27ac ChIP-seq Reveals Claudin-1 as a Biomarker for Radiation Resistance in Colorectal Cancer

et al. 2021

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Background Colorectal cancer (CRC) represents the third most common malignant tumor in the worldwide. Radiotherapy is the common therapeutic treatment for CRC, but radiation resistance is often encountered. ChIP-seq of Histone H3K27 acetylation (H3K27ac) has revealed enhancers that play an important role in CRC. This study examined the relationship between an active CRC enhancer and claudin-1 (CLDN1), and its effect on CRC radiation resistance. Methods The target CRC genes of active enhancers were obtained from public H3K27ac ChIP-seq, and the genes highly expressed in radio-resistant CRC were screened and intersected with enhancer-driven genes. The clinical roles of CLDN1 in radiation resistance were examined using the t-test, standard mean deviation (SMD), summary receiver operating characteristic curve and Kaplan-Meier curves. The co-expressed genes of CLDN1 were calculated using Pearson Correlation analysis, and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes and Gene Set Variation Analysis (GSVA) analyses were used to examine the molecular mechanisms of CLDN1. Results Total 13 703 CRC genes were regulated by enhancers using 58 H3K27ac ChIP-seq. Claudin-1 (CLDN1) was enhancer-driven and notably up-regulated in CRC tissues compared to non-CRC controls, with a SMD of 3.45 (95 CI % = .56-4.35). CLDN1 expression was increased in radiation-resistant CRC with a SMD of .42 (95% CI = .16-.68) and an area under the curve of .74 (95% CI = .70-.77). The cell cycle and immune macrophage levels were the most significant pathways associated with CLDN1. Conclusion CLDN1 as an enhancer-regulated gene that can boost radiation resistance in patients with CRC.

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“…On the other hand, the biotransformation of cranberry proanthocyanidins by this bacterium resulted in higher cytotoxicity against HepG2 hepatocellular cell line compared to the parent extract, by Apaf-1 activation and mitochondria-dependent apoptotic mechanism via ATP depletion (Rupasinghe et al 2019 ). Moreover, metabolites derived from Lactobacillus plantarum (LDMs) sensitized 5-FU-resistant HCT-116 cells to chemotherapy through downregulating the expression of claudin-1 (CLDN-1), a tight junction transmembrane protein (An & Ha, 2020 ). Baicalein, a byproduct of the transformation of an anti-inflammatory component of herb Scutellaria baicalensis by the intestinal microbiota, inhibited gut inflammation by reducing the levels of inflammatory cytokines (IL-2, IL-6) and induced cellular death of cancer cells (Wang et al 2020 ).…”

Section: Anti-cancer Activity Of Bacterial Extractsmentioning

confidence: 99%

Therapeutic applications and biological activities of bacterial bioactive extracts

et al. 2021

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Bacteria are rich in a wide variety of secondary metabolites, such as pigments, alkaloids, antibiotics, and others. These bioactive microbial products serve a great application in human and animal health. Their molecular diversity allows these natural products to possess several therapeutic attributes and biological functions. That’s why the current natural drug industry focuses on uncovering all the possible ailments and diseases that could be combated by bacterial extracts and their secondary metabolites. In this paper, we review the major utilizations of bacterial natural products for the treatment of cancer, inflammatory diseases, allergies, autoimmune diseases, infections and other diseases that threaten public health. We also elaborate on the identified biological activities of bacterial secondary metabolites including antibacterial, antifungal, antiviral and antioxidant activities all of which are essential nowadays with the emergence of drug-resistant microbial pathogens. Throughout this review, we discuss the possible mechanisms of actions in which bacterial-derived biologically active molecular entities could possess healing properties to inspire the development of new therapeutic agents in academia and industry.

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Lactobacillus-derived metabolites enhance the antitumor activity of 5-FU and inhibit metastatic behavior in 5-FU-resistant colorectal cancer cells by regulating claudin-1 expression

Cited by 15 publications

References 48 publications

Patient-Derived Organoid Model in the Prediction of Chemotherapeutic Drug Response in Colorectal Cancer

Patient-Derived Organoid Model in the Prediction of Chemotherapeutic Drug Response in Colorectal Cancer

Active Enhancer Assessment by H3K27ac ChIP-seq Reveals Claudin-1 as a Biomarker for Radiation Resistance in Colorectal Cancer

Therapeutic applications and biological activities of bacterial bioactive extracts

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