Baicalein Acts against Candida albicans by Targeting Eno1 and Inhibiting Glycolysis

Li, Liping; Lu, Hui; Zhang, Xuan; Whiteway, Malcolm; Wu, Hao; Tan, Shanlun; Zang, Jianye; Tian, Shujuan; Zhen, Cheng; Meng, Xianlei; Li, Wanqian; Zhang, Dazhi; Zhang, Min; Jiang, Yuanying

doi:10.1128/spectrum.02085-22

Cited by 15 publications

(25 citation statements)

References 63 publications

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“…Enolase 1 (ENO 1) is a type of enolase isozyme that promotes the formation of phosphoenolpyruvate via catalysis by 2-phospho-glycerate and generates ATP during glycolysis ( 4 ). It is a glycolytic enzyme with multiple functions in bacterial and fungal infections; autoantigen activities; and occurrence, development and metastasis of cancer ( 5 , 6 ). ENO1 was also reported to be a plasminogen receptor involved in the invasion and metastasis of pancreatic ductal adenocarcinoma (PDA) cells ( 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

ENO1 contributes to 5-fluorouracil resistance in colorectal cancer cells via EMT pathway

Zhong

Wang

et al. 2022

Front. Oncol.

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IntroductionChemoresistance is a major barrier in the treatment of colorectal cancer (CRC) and many other cancers. ENO1 has been associated with various biological characteristics of CRC. This study aimed to investigate the function of ENO1 in regulating 5-Fluorouracil (5-FU) resistance in CRC.MethodsENO1 level in 120 pairs of tumor tissues and adjacent normal tissues was examined by immunohistochemistry, and the correlation between ENO1 expression and prognosis was explored by survival analysis. Its role and potential mechanisms in regulating 5-FU resistance in CRC were studied by Western blotting, MTT assay, colony formation assay and transwell invasion assay. Murine xenograft assay was implied to verify the results in vivo.ResultsOur study indicated that ENO1 was elevated in CRC tissues and was associated with poor patient prognosis. High levels of ENO1 expression were detected as a significant influencing factor for overall survival. Furthermore, ENO1 expression was found to have increased in drug-resistant cells (HCT116/5-FU and SW620/5-FU) constructed by increasing concentrations of 5-FU. Knockdown of ENO1 markedly increased the drug susceptibility and inhibited the proliferation and migration ability of HCT116/5-FU and SW620/5-FU cells. It was found that down-regulation of ENO1 inhibited the epithelial-mesenchymal transformation (EMT) signaling process. Finally, a murine xenograft assay verified that the depletion of ENO1 alleviated 5-FU resistance.ConclusionThis study identified that ENO1 regulated 5-FU resistance via the EMT pathway and may be a novel target in the prevention and treatment of 5-FUresistant CRC.

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Section: Introductionmentioning

confidence: 99%

ENO1 contributes to 5-fluorouracil resistance in colorectal cancer cells via EMT pathway

Zhong

Wang

et al. 2022

Front. Oncol.

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“…To evaluate our initial hypothesis on the ecological function of promiscuous enzymes of wood-decaying fungi as detoxification enzymes, we tested antifungal activity of the precursor phytochemicals ( 1 , 2 , 11 , and 12 ) and their xylosylated metabolites. Compounds 2 , 11 , and 12 were known to exhibit toxicity against broad spectrum of fungi ( 34 , 65 ). However, they were not inhibitory at concentrations up to 5.7 μM and showed only weak inhibition against L. brumalis at 14.3 μM, while itraconazole, a broad-spectrum antifungal drug used as a positive control, showed a significant growth inhibition in a lower concentration ( SI Appendix , Fig.…”

Section: Resultsmentioning

confidence: 99%

Qualitative metabolomics-based characterization of a phenolic UDP-xylosyltransferase with a broad substrate spectrum from Lentinus brumalis

Jeong

Kim

Son

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Wood-decaying fungi are the major decomposers of plant litter. Heavy sequencing efforts on genomes of wood-decaying fungi have recently been made due to the interest in their lignocellulolytic enzymes; however, most parts of their proteomes remain uncharted. We hypothesized that wood-decaying fungi would possess promiscuous enzymes for detoxifying antifungal phytochemicals remaining in the dead plant bodies, which can be useful biocatalysts. We designed a computational mass spectrometry–based untargeted metabolomics pipeline for the phenotyping of biotransformation and applied it to 264 fungal cultures supplemented with antifungal plant phenolics. The analysis identified the occurrence of diverse reactivities by the tested fungal species. Among those, we focused on O -xylosylation of multiple phenolics by one of the species tested, Lentinus brumalis . By integrating the metabolic phenotyping results with publicly available genome sequences and transcriptome analysis, a UDP-glycosyltransferase designated UGT66A1 was identified and validated as an enzyme catalyzing O -xylosylation with broad substrate specificity. We anticipate that our analytical workflow will accelerate the further characterization of fungal enzymes as promising biocatalysts.

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“…Molecular docking is used to explore the mode and strength of biomolecular interactions at the molecular level ( Li et al, 2022a ). Here, we interpreted the binding strength and mechanism of baicalein and nine CTGs through molecular docking using the AutoDock Vina program.…”

Section: Resultsmentioning

confidence: 99%

“…Given multidirectional pharmacology and system biology, network pharmacology is an emerging subject of systematic drug research. The associations among a drug, target, and disease are comprehensively analyzed by data mining at the molecular level, and potential targets of a drug are predicted ( Li et al, 2022a ). To date, network pharmacology has been widely applied to explore the mechanism of compounds in traditional Chinese medicine (TCM).…”

Section: Introductionmentioning

confidence: 99%

Therapeutic mechanism of baicalein in peritoneal dialysis-associated peritoneal fibrosis based on network pharmacology and experimental validation

Lu,

Wu,

Jiang

et al. 2023

Front. Pharmacol.

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Baicalein (5,6,7-trihydroxyflavone) is a traditional Chinese medicine with multiple pharmacological and biological activities including anti-inflammatory and anti-fibrotic effects. However, whether baicalein has a therapeutic impact on peritoneal fibrosis has not been reported yet. In the present study, network pharmacology and molecular docking approaches were performed to evaluate the role and the potential mechanisms of baicalein in attenuating peritoneal dialysis-associated peritoneal fibrosis. The results were validated in both animal models and the cultured human mesothelial cell line. Nine intersection genes among baicalein targets and the human peritoneum RNA-seq dataset including four encapsulating peritoneal sclerosis samples and four controls were predicted by network analysis. Among them, MMP2, BAX, ADORA3, HIF1A, PIM1, CA12, and ALOX5 exhibited higher expression in the peritoneum with encapsulating peritoneal sclerosis compared with those in the control, which might be crucial targets of baicalein against peritoneal fibrosis. Furthermore, KEGG and GO enrichment analyses suggested that baicalein played an anti-peritoneal fibrosis role through the regulating cell proliferation, inflammatory response, and AGE-RAGE signaling pathway. Moreover, molecular docking analysis revealed a strong potential binding between baicalein and MMP2, which was consistent with the predictive results. Importantly, using a mouse model of peritoneal fibrosis by intraperitoneally injecting 4.25% glucose dialysate, we found that baicalein treatment significantly attenuated peritoneal fibrosis, as evident by decreased collagen deposition, protein expression of α-SMA and fibronectin, and peritoneal thickness, at least, by reducing the expression of MMP2, suggesting that baicalein may have therapeutic potential in suppressing peritoneal dialysis-related fibrosis.

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Baicalein Acts against Candida albicans by Targeting Eno1 and Inhibiting Glycolysis

Abstract: Baicalein (BE) is a promising antifungal agent which has been well characterized, but its target protein is still undiscovered. The protein Eno1 plays a crucial role in the survival of Candida albicans .

Cited by 15 publications

References 63 publications

ENO1 contributes to 5-fluorouracil resistance in colorectal cancer cells via EMT pathway

ENO1 contributes to 5-fluorouracil resistance in colorectal cancer cells via EMT pathway

Qualitative metabolomics-based characterization of a phenolic UDP-xylosyltransferase with a broad substrate spectrum from Lentinus brumalis

Therapeutic mechanism of baicalein in peritoneal dialysis-associated peritoneal fibrosis based on network pharmacology and experimental validation

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