Inhibitory effects of flavonoids on glucose transporter 1 (GLUT1): From library screening to biological evaluation to structure-activity relationship

Sun, Yanhong; Duan, Xinbin; Wang, Fenghe; Tan, Huixin; Hu, Jiahuan; Bai, Wanting; Wang, Xinbo; Wang, Baolian; Hu, Jiye

doi:10.1016/j.tox.2023.153475

Cited by 7 publications

(5 citation statements)

References 39 publications

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“…The data in Table 5 show that Nypa fruticans Wurmb fruit can increase the repair of islets of Langerhans, and increase beta cells, as an indicator of the improved function of insulin produced by beta cells. From a theoretical perspective, flavonoids or antioxidant compound that Nypa fruticans Wurmb have can increase GLUT translocation activity, glucose uptake by tissues, and liver enzyme activity, causing a decrease in apoptosis and inhibition of tyrosine kinase to prevent an increase in diabetes mellitus (Sun et al 2023). This property aligns with the data in Table 4, where several antioxidant compounds possessed by Nypa fruticans Wurmb have bioactivity with receptor kinases, ion channel modulators and nuclear receptor ligands, protease inhibitors, and enzyme inhibitors.…”

Section: Discussionsupporting

confidence: 78%

Characteristic and bioactivities value of Nypa fruticans from coastal area in West Aceh District, Indonesia as a candidate antidiabetic agent

FITRI,

YUSNI,

SURYADI

et al. 2023

Biodiversitas

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Abstract. Fitri Y, Yusni Y, Suryadi T, Mudatsir M. 2023. Characteristic and bioactivities value of Nypa fruticans from coastal area in West Aceh District, Indonesia as a candidate antidiabetic agent. Biodiversitas 24: 5260-5269. Nypa fruticans Wurmb is a functional plant that grows on the coasts of Indonesia, produced food and has health benefits. It has been believed for generations that Nypa fruticans Wurmb has potential as an antidiabetic, although a complete study is needed. This research aimed to evaluate the potential of the fruit of the Nypa fruticans Wurmb plant as an antidiabetic based on its characteristic values and pancreatic histopathology. The fruit was evaluated for phytochemical, tannin quantity, chemical compound determination, and confirmation of bioactivity. Antidiabetic properties were evaluated for pancreatic histopathology in an animal model. Nypa fruticans Wurmb contains polyphenols, tannins, saponins, triterpenoids, alkaloids and flavonoids, with a tannins quantity of 11.10 mg/AT/g extract. Furthermore, it contains antioxidant, and anti-inflammatory compounds, including the dominant 2,3-Butanediol (CAS) Butane-2,3-diol, Propane-1,1-diol diacetate, 4H-Pyran-4-one, 2,3-dihydro-3,5-dihydrox, and 9,12-Octadecadienoic acid (Z,Z)- (CAS) Li. In addition, it has excellent bioactivity against nuclear receptor ligands, protease inhibitors, and enzyme inhibitors as an indicator of binding affinity with hot cells. Nypa fruticans Wurmb can increase beta cells, and expand the islets of Langerhans. The Nypa fruticans Wurmb, besides containing antioxidant and inflammatory compounds, has hight bioactivity, wich increases the frequency of beta cells and improves pancreatic islets of Langerhans repair in diabetic models.

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Section: Discussionsupporting

confidence: 78%

Characteristic and bioactivities value of Nypa fruticans from coastal area in West Aceh District, Indonesia as a candidate antidiabetic agent

FITRI,

YUSNI,

SURYADI

et al. 2023

Biodiversitas

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“…One of the main mechanisms reported to be involved is the inhibition of glucose uptake, mainly through decreased expression of the facilitative glucose transporter GLUT1. Indeed, LUT has been recently highlighted as one of the phenolic compounds with the strongest GLUT1 inhibitory activity in human embryonic kidney cells (HEK293T) that present stable expression of this receptor [31]. Moreover, some phenols such as curcumin, oroxylin A, and resveratrol were reported to directly interfere with glycolytic enzymes and glycolytic flux [29].…”

Section: Discussionmentioning

confidence: 99%

Metabolomics Insights into the Differential Response of Breast Cancer Cells to the Phenolic Compounds Hydroxytyrosol and Luteolin

et al. 2023

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The aim of this study was to investigate the effects of two phenolic compounds found in extra virgin olive oil, hydroxytyrosol (HT) and luteolin (LUT), on the metabolism of breast cancer (BC) cells of different molecular subtypes. An untargeted metabolomics approach was used to characterize the metabolic responses of both triple-negative MDA-MB-231 cells and hormone-responsive MCF-7 cells to treatment with these phenols. Notably, while some effects were common across both cell types, others were dependent on the cell type, highlighting the importance of cellular metabolic phenotype. Common effects included stimulation of mitochondrial metabolism, acetate production, and formate overflow. On the other hand, glucose metabolism and lactate production were differentially modulated. HT and LUT appeared to inhibit glycolysis and promote the hexosamine biosynthetic pathway in MDA-MB-231 cells, while MCF-7 cells exhibited higher glycolytic flux when treated with phenolic compounds. Another significant difference was observed in lipid metabolism. Treated MDA-MB-231 cells displayed increased levels of neutral lipids (likely stored in cytosolic droplets), whereas treatment of MCF-7 cells with HT led to a decrease in triacylglycerols. Additionally, glutathione levels increased in MDA-MB-231 cells treated with HT or LUT, as well as in MCF-7 cells treated with LUT. In contrast, in HT-treated MCF-7 cells, glutathione levels decreased, indicating different modulation of cellular redox status. Overall, this work provides new insights into the metabolic impact of HT and LUT on different BC cell subtypes, paving the way for a better understanding of the nutritional relevance of these phenolic compounds in the context of BC prevention and management.

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“…3,5,6,7,3',4'-hexamethoxyflavone and 3,5,6,7,8,3',4'-heptamethoxyflavone also play an important role in breast cancer ( 10 ). Sinensetin showed strong sensitization in HepG2 cells, which caused the cell viability curve to decrease sharply ( 13 - 15 ). The current study suggests that if more toxicological and in vivo studies are conducted, sinensetin have the potential to become a candidate for the treatment of gallbladder adenocarcinoma ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

Sinensetin suppresses breast cancer cell progression via Wnt/β-catenin pathway inhibition

Zhu,

Meng,

Wei

et al. 2024

Transl Cancer Res

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Background Although there are many treatments for breast cancer, such as surgery, radiotherapy, chemotherapy, estrogen receptor antagonists, immune checkpoint inhibitors and so on. However, safer and more effective therapeutic drugs for breast cancer are needed. Sinensetin, a safer therapeutic drugs, come from citrus species and medicinal plants used in traditional medicine, while its role and underlying mechanism in breast cancer remain unclear. Our study aimed to investigate the role and mechanism of sinensetin in breast cancer. Methods Cell Counting Kit-8 (CCK-8) was used to determine the safe concentration of sinensetin in MCF-10A, MCF7 and MDA-MB-231 cells; 120 μM sinensetin was used in subsequent experiments. Real time polymerase chain reaction (RT-PCR), Western blotting, Terminal Deoxynucleotidyl Transferase mediated dUTP Nick-End Labeling (TUNEL) apoptosis assay, Transwell invasion assay and Clone formation assay were used in this study to determine cell viability, mRNA expression, protein levels, apoptosis, proliferation, invasion and so on. Results Herein, our results showed that 120 μM sinensetin suppressed the cell viability and promoted apoptosis of MCF7 and MDA-MB-231 cells. Treatment with 120 µM sinensetin for 24 h showed no significant toxicity to normal mammary cells; 120 μM sinensetin decreased cell proliferation, invasion, and epithelial-mesenchymal transition (EMT), and downregulated β-catenin, lymphatic enhancing factor 1 (LEF1), T-cell factor (TCF) 1/TCF7, and TCF3/TCF7L1 expression in MCF7 and MDA-MB-231 cells. The Wnt agonist SKL2001 reversed the inhibitory effect of sinensetin on cell survival, metastasis, and EMT. Sinensetin-induced downregulation of β-catenin, LEF1, and TCF1/TCF7 expression were upregulated by SKL2001 in MCF7 and MDA-MB-231 cells. Conclusions In summary, sinensetin suppressed the metastasis of breast cancer cell via inhibition of Wnt/β-catenin pathway and there were no adverse effects on normal breast cells. Our study confirmed the role of sinensetin in breast cancer cells and provided a better understanding of the underlying mechanism.

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Inhibitory effects of flavonoids on glucose transporter 1 (GLUT1): From library screening to biological evaluation to structure-activity relationship

Cited by 7 publications

References 39 publications

Characteristic and bioactivities value of Nypa fruticans from coastal area in West Aceh District, Indonesia as a candidate antidiabetic agent

Characteristic and bioactivities value of Nypa fruticans from coastal area in West Aceh District, Indonesia as a candidate antidiabetic agent

Metabolomics Insights into the Differential Response of Breast Cancer Cells to the Phenolic Compounds Hydroxytyrosol and Luteolin

Sinensetin suppresses breast cancer cell progression via Wnt/β-catenin pathway inhibition

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